Levels Of Keratinocyte Growth Factor Research Articles

Effect of applying Lactiplantibacillus plantarum subsp. plantarum N793 to the scalps of men and women with thinning hair: a randomized, double-blind, placebo-controlled, parallel-group study.

Lactiplantibacillus plantarum subsp. plantarum N793 (N793) is a lactic acid bacterium (LAB) isolated from corn. We previously showed that N793 increases the level of keratinocyte growth factor, which is required for hair growth, in the culture supernatant of human follicle dermal papilla cells. Additionally, an open-label, single-arm study reported that applying a lotion containing N793 to the scalp for 24 weeks improved hair density in men and women with thinning hair. The present study was a double-blind, placebo-controlled, parallel-group study aimed at verifying the efficacy of N793 for thinning hair. A lotion containing N793, and a control lotion (placebo) were applied once daily for 24 weeks to 104 healthy Japanese men and women. Analysis of all participants revealed no difference in hair density between the N793 and placebo groups. However, an additional analysis limited to participants with relatively mild progression of thinning hair showed a significantly better hair density in the N793 group than in the placebo group. These findings suggest that topical application of N793 improves thinning hair in men and women when the condition's progression is relatively mild.

Therapeutic effects of mesenchymal stem cells-conditioned medium derived from suspension cultivation or silymarin on liver failure mice.

Common treatments of liver disease failed to meet all the needs in this important medical field. It results in an urgent need for proper some new adjuvant therapies. Mesenchymal stem cells (MSCs) and their derivatives are promising tools in this regard. We aimed to compare the Silymarin, as traditional treatment with mesenchymal stem cell conditioned medium (MSC-CM), as a novel strategy, both with therapeutic potentialities in term of liver failure (LF) treatment. Mice models with liver failure were induced with CCl4 and were treated in the groups as follows: normal mice receiving DMEM-LG medium as control, LF-mice receiving DMEM-LG medium as sham, LF-mice receiving Silymarin as LF-SM, and LF-mice receiving MSC sphere CM as LF-MSC-CM. Biochemical, histopathological, molecular and protein level parameters were evaluated using blood and liver samples. Liver enzymes, MicroRNA-122 values as well as necrotic score were significantly lower in the LF-SM and LF-MSC-CM groups compared to sham. LF-SM showed significantly higher level of total antioxidant capacity and malondialdehyde than that of LF-MSC-CM groups. Sph-MSC-CM not only induced more down-regulated expression of fibrinogen-like protein 1 and receptor interacting protein kinases1 but also led to higher expression level of keratinocyte growth factor. LF-MSC-CM showed less mortality rate compared to other groups. Hepato-protective potentialities of Sph-MSC-CM are comparable to those of Silymarin. More inhibition of necroptosis/ necrosis and inflammation might result in rapid liver repair in case of MSC-CM administration.

Protective effects of pre-treatment with exogenous porcine glucagon-like peptide-2 and its microspheres of piglets with lipopolysaccharide-induced intestinal inflammation

Context Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can accelerate intestinal development and recovery from injury. However, the half-life of GLP-2 is short, thus it must be administered frequently. Moreover, its effects during weaning are unclear. Aims We tested the effects of porcine GLP-2 (pGLP-2) and pGLP-2 microspheres on lipopolysaccharide (LPS)-induced intestinal inflammation in weaning piglets. Methods Eighteen female weaning piglets aged 21 days (5.38 ± 0.72 kg initial bodyweight) were randomly assigned to three treatment groups: (1) control, (2) GLP-2, and (3) GLP-2 microsphere (MS) group. Control piglets were injected intraperitoneally with 3 mL of saline solution from Days 1 to 7, GLP-2 piglets were injected intraperitoneally with 100 μg pGLP-2/kg bodyweight from Days 1 to 7, and MS piglets were injected intraperitoneally with 200 mg GLP-2 microspheres on Day 1 and with 3 mL saline solution from Days 2 to 7. On Day 8, all piglets were injected with 100 μg LPS/kg bodyweight. Key results Piglets in the GLP-2 and MS groups showed markedly increased average daily weight gain on Day 7, decreased serum myeloperoxidase, LPS and keratinocyte growth factor levels, and increased serum interleukin-10 levels compared with the control group. In addition, the GLP-2 group showed decreased myeloperoxidase content in the duodenum and ileum, and reduced caspase-3 activity in the duodenum and jejunum, whereas MS piglets showed decreased myeloperoxidase levels and suppressed caspase-3 activity in the duodenum and jejunum. Moreover, administration of pGLP-2 or pGLP-2 microspheres resulted in decreased interleukin-8 and interferon-γ mRNA expression levels in the jejunum, as compared with the control group. Conclusions Our results indicated that pGLP-2 promotes growth, and ameliorates LPS-induced serum and intestinal inflammatory responses in piglets. Furthermore, pGLP-2 microspheres can achieve similar therapeutic effects as pGLP-2 under the premise of fewer injections. Implications pGLP-2 microspheres have considerable potential for the treatment of weaning-induced intestinal inflammation in piglets.

Effect of Taspine hydrochloride on the repair of rat skin wounds by regulating keratinocyte growth factor signal

ABSTRACT To explore the regulation of keratinocyte growth factor (KGF) in the process of repairing rat skin wounds by taspine hydrochloride (TA/HCl), 45 male Sprague-Dawley (SD) rats were purchased and divided into an experimental group, a dimethyl sulfoxide (DMSO) control group, and a basic fibroblast growth factor (bFGF) control group, each with 15 only. A back trauma model was innovatively adopted to prevent rats from biting and contaminating. The wound healing time and healing rate of the rat, and the Hydroxyproline (Hyp) and KGF expressions were observed. Morphological changes of wound tissue and the number of capillaries were observed after hematoxylin-eosin (HE) staining. The results showed that wound healing rate of experimental group and bFGF group was significantly higher than that of DMSO group (P < 0.05) after 2–15 days, and wound healing time of experimental group was 18 days, which was significantly lower than that of the DMSO group (P < 0.05). Expression levels of Hyp and KGF in the granulation tissue of rats in the experimental group were much higher than those in the DMSO control group after trauma (P < 0.05). In early stage of wound tissue repair, the number of new capillaries formed in experimental group was significantly higher than that in DMSO control group (P < 0.05). In summary, this study innovatively focused on KGF. The mechanism of TA/HCL promoting rat skin wound healing was closely related to KGF.

Plasma Levels of Keratinocyte Growth Factor Are Significantly Elevated for 5 Weeks After Minimally Invasive Colorectal Resection Which May Promote Cancer Recurrence and Metastasis.

Background: Human Keratinocyte Growth Factor (KGF) is an FGF family protein produced by mesenchymal cells. KGF promotes epithelial cell proliferation, plays a role in wound healing and may also support tumor growth. It is expressed by some colorectal cancers (CRC). Surgery's impact on KGF levels is unknown. This study's purpose was to assess plasma KGF levels before and after minimally invasive colorectal resection (MICR) for CRC.Aim: To determine plasma KGF levels before and after minimally invasive colorectal resection surgery for cancer pathology.Method: CRC MICR patients (pts) in an IRB approved data/plasma bank were studied. Pre-operative (pre-op) and post-operative (post-op) plasma samples were taken/stored. Late samples were bundled into 7 day blocks and considered as single time points. KGF levels (pg/ml) were measured via ELISA (mean ± SD). The Wilcoxon paired t-test was used for statistical analysis.Results: Eighty MICR CRC patients (colon 61%; rectal 39%; mean age 65.8 ± 13.3) were studied. The mean incision length was 8.37 ± 3.9 and mean LOS 6.5 ± 2.6 days. The cancer stage breakdown was; I (23), II (26), III (27), and IV (4). The median pre-op KGF level was 17.1 (95 %CI: 14.6–19.4; n = 80); significantly elevated (p < 0.05) median levels (pg/ml) were noted on post-op day (POD) 1 (23.4 pg/ml; 95% CI: 21.4–25.9; n = 80), POD 3 (22.5 pg/ml; 95% CI: 20.7–25.9; n = 76), POD 7–13 (21.8 pg/ml; 95% CI: 17.7–25.4; n = 50), POD 14–20 (20.1 pg/ml; 95% CI: 17.1–23.9; n = 33), POD 21–27 (19.6 pg/ml; 95% CI: 15.2–24.9; n = 15) and on POD 28–34 (16.7 pg/ml; 95% CI: 14.0–25.8; n = 12).Conclusion: Plasma KGF levels were significantly elevated for 5 weeks after MICR for CRC. The etiology of these changes is unclear, surgical trauma related acute inflammatory response and wound healing process may play a role. These changes, may stimulate angiogenesis in residual tumor deposits after surgery.

Keratinocyte Growth Factor-Based Strategies for Wound Re-Epithelialization.

Wound re-epithelialization is a dynamic process that comprises the formation of new epithelium through an active signaling network between several growth factors (GFs) and various cell types. The main players are keratinocytes (KCs) that migrate from the wound edges over the wound bed to restore the epidermal barrier. One of the most important molecules involved in the re-epithelialization process is keratinocyte growth factor (KGF), a central player on promoting both migration and proliferation of KCs. Stromal cells, such as dermal fibroblasts, are the main producers of this factor, acting on KCs through paracrine signaling. Multiple therapeutic strategies to deliver KGF have been proposed to boost wound healing by targeting re-epithelialization. Different approaches have been explored to attain that purpose, such as topical application of this factor, controlled release of KGF from different biomaterials (hydrogels, nanoparticles, and membranes), and also gene delivery techniques. Among these strategies, KGF release via biomaterials- and genetic-based strategies shows great effectiveness in maintaining sustained KGF levels at the wound site, which is reflected in an efficient wound closure. Under this scope, this review aims not only to elucidate the potential of KGF in wound re-epithelialization but also to describe the underlying mechanism of action and further explore the therapeutic approaches using this GF. Impact statement Upon skin injury, wound re-epithelialization is one of the major milestones of the healing process. This is especially difficult to achieve on hard-to-heal wounds that are often open for long periods, as the dysregulation of the growth factors involved in this response contributes to an impaired proliferation and migration of keratinocytes. Keratinocyte growth factor (KGF) plays a central role in this problematic, as it is a potent factor that in the normal healing scenario promotes direct proliferation and migration of epidermal cells, consequently impacting re-epithelialization. Under this context, in the first part of this review, the process of wound healing and the mechanism of action of KGF are described. In the second part, various KGF delivery approaches aiming at skin re-epithelialization are reported and actively discussed. In this sense, it is herein highlighted the role of KGF in wound re-epithelialization and provided a critical overview of potential therapeutic strategies exploited so far.

Role of bone marrow-derived mesenchymal stem cells in alleviating pulmonary epithelium damage and extracellular matrix remodeling in a rat model of lung fibrosis induced by amiodarone

ABSTRACT The therapeutic role of mesenchymal stem cells (MSCs) in cases of amiodarone (AD) induced pulmonary fibrosis (PF) has not been well studied. Also, the period required by MSCs to attain full therapeutic effectiveness has not yet been assessed. We investigated the potential curative effect of bone marrow-derived MSCs (BM-MSCs) and conditioned media (CM) from BM-MSCs on AD induced PF by focusing on pulmonary epithelium injury and repair, and extracellular matrix (ECM) remodeling. We used 64 Wistar rats divided into eight groups: negative control group; PF group; three PF groups treated with BM-MSCs for 1, 2 or 4 months; and three PF groups treated with CM for 1, 2 and 4 months. Serum levels of Clara cell secretory protein (CC16) and keratinocyte growth factor (KGF) were measured. Gene expression of type I collagen (COL1A1) and connective tissue growth factor (CTGF) was evaluated in pulmonary tissue. Treatment of PF challenged rats with BM-MSCs or CM caused reduced CC16 levels, increased KGF levels, reduced expression of COL1A1 and CTGF, histological improvement following lung injury, and decreased collagen accumulation. Treatment with BM-MSCs exhibited greater amelioration of PF than CM. BM-MSCs or CM treatment for 2 and 4 months exhibited better resolution of fibrosis than treatment for 1 month. BM-MSCs are promising for treating PF due to their attenuation of ECM deposition in addition to alleviating pulmonary epithelium damage and initiating its repair.

The proliferative and anti-apoptosis functions of KGF/KGFR contributes to bronchial epithelial repair in asthma

This study aimed to investigate the effect of keratinocyte growth factor (KGF) on the apoptosis, proliferation, damage repair, intercellular adhesion, and inflammatory cytokine release of cultured 16HBE 14o-bronchial ECs in vitro. Bronchial epithelial cells (ECs) from all subjects were obtained by bronchoscopic brushing. The expression levels of KGF and its receptor KGFR in collected cells were determined using RT-qPCR and Western blotting. The apoptosis and adhesion molecules expression by KGF administration were determined using flow cytometry and Western blotting. This occurred when 16HBE 14o-cell lines cultured and were exposed to interferon-γ (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in vitro. The role of KGF on proliferation and damage repair were analyzed using CCK-8, EdU and wound closure assays after 16HBE 14o-cells were scraped. The effect of KGF on the release of inflammation related cytokines by damaged ECs was measured using ELISA kits. Compared with healthy controls, the KGF and KGFR expression and apoptosis significantly increased in collected cells from asthma patients. In vitro, treatment of KGF may limit IFN-γ and TNF-α induced apoptosis by inhibiting apoptosis-associated markers in the TNF signaling pathway. Besides, KGF could limit the release of TSLP, IL-25 and IL-33 by damaged 16HBE 14o-cells. On the contrary, KGF could promote the intercellular adhesion and wound closure of cultured 16HBE 14o-cells via the increased expression level of intercellular junction proteins ICAM-1, β-catenin, E-cad, and Dsc3. In conclusion, KGF and KGFR may help bronchial ECs repair in asthma via the inhibition apoptosis of ECs while the promotion of proliferation and migration of ECs.

Emerging role of dermal compartment in skin pigmentation: comprehensive review.

The variations in human skin colour mainly occur due to differences in the distribution of melanin pigment throughout the body, synthesized by epidermal melanocytes which are further taken up by keratinocytes present in epidermis. Recently, it has been discovered that besides these cells, dermis derived fibroblast factors also play a prominent role in regulating skin pigmentation. There exists a signal crosstalk between epidermal melanocytes, keratinocytes and dermal fibroblasts and any impairment in these signalling pathways may give rise to pigmentary disorders. Vitiligo is a hypopigmentary disorder and alteration in the expression level of several fibroblast-specific factors has been reported in the lesional skin of vitiligo patients. In such patients, there is decrease in the expression levels of factors such as basic fibroblast growth factor, stem cell factor (SCF) and keratinocyte growth factor (KGF) along with a steep increase in the expression levels of Dickkopf 1. Patients affected with hyperpigmentary disorder like melasma exhibit a marked increase in SCF and KGF expression levels leading to increase in melanin production and those affected with solar lentigo experience upregulation in the expression levels of SCF, KGF and HGF (hepatocyte growth factor). Hence, we conclude that new therapeutic strategies can be adopted to cure these pigmentary disorders by targeting factors involved in crosstalk signalling between epidermal melanocytes, keratinocytes and dermal fibroblasts.

Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation‑induced corneal neovascularization.

Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), two paracrine growth factors, modulate corneal epithelial cell metabolism, apoptosis and survival. Vascular endothelial growth factor (VEGF) serves as a proangiogenic factor in corneal neovascularization (CNV), which is a major cause of vision impairment and corneal blindness. The aim of the present study was to evaluate the ability of HGF and KGF to influence VEGF and its receptor, kinase insert domain receptor (Flk‑1) in corneal injury and CNV in rats induced by ultraviolet radiation (UVR). An UVR‑induced corneal injury rat model was successfully established to characterize the expression patterns of KGF, HGF, VEGF and Flk‑1 in corneal tissues. Corneal epithelial cells were extracted and treated with small interfering RNAs (siRNAs) targeting KGF, HGF or both (si‑KGF, si‑HGF or si‑HGF/KGF). The effects of HGF and KGF were examined through detection of the expression of KGF, HGF, VEGF and Flk‑1, and the evaluation of cell proliferation, cell cycle and cell apoptosis. The expression levels of KGF, HGF, VEGF and Flk‑1 in corneal tissues were increased in the rat model. In the cell experiments, the transfection of si‑HGF/KGF resulted in reductions in VEGF, Flk‑1, KGF and HGF. In addition, decreased cell proliferation and elevated cell apoptosis were found in the corneal epithelial cells from the rat model following KGF and HGF gene silencing. Taken together, these findings suggest that HGF and KGF gene silencing inhibits UVR‑induced corneal epithelial proliferation and CNV and may function as novel targets for corneal wound healing.

Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway.

Acute lung injury (ALI) is a common, costly and potentially lethal disease with characteristics of alveolar‑capillary membrane disruption, pulmonary edema and impaired gas exchange due to increased apoptosis and pulmonary inflammation. There is no effective and specific therapy for ALI; however, mesenchymal stem cells (MSCs) have been demonstrated to be a potential option. Lipopolysaccharide (LPS) is a highly proinflammatory molecule that is used to mimic an invivo inflammatory and damaged state invitro. The present study investigated the effect of bone marrow‑derived MSCs on an LPS‑induced alveolar epithelial cell (A549cell line) injury and its underlying mechanisms by a Transwell system. It was identified that a high LPS concentration caused a decrease in cell viability, increases in apoptosis, inflammatory cytokine release and NF‑κB activity, disruption of the caspase‑3/Bcl‑2 ratio, upregulation of Toll‑like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and toll‑interleukin‑1 receptor domain‑containing adaptor inducing interferon (TRIF) expression, and facilitation of TLR4/MyD88 and TLR4/TRIF complex formation in A549 cells. Coculture with MSCs attenuated all of these activities induced by LPS in A549 cells. In addition, an increased level of keratinocyte growth factor (KGF) and angiopoietin‑1 (ANGPT1) secretion from MSCs was observed under inflammatory stimulation. KGF and/or ANGPT1 neutralizing antibodies diminished the beneficial effect of MSC conditioned medium. These data suggest that MSCs alleviate inflammatory damage and cellular apoptosis induced by LPS in A549 cells by modulating TLR4 signals. These changes may be partly associated with an increased secretion of KGF and ANGPT1 from MSCs under inflammatory conditions. These data provide the basis for development of MSC‑based therapies for ALI.

KGF Enhances Oral Epithelial Adhesion and Rete Peg Elongation via Integrins

Oral epithelial adhesion to the lamina propria underlies the physiologic function of the oral mucosa and contributes to resisting bacterial invasion, preventing body fluid loss, and maintaining routine chewing; thus, understanding the factors that positively influence oral epithelial adhesion is a research topic of great interest. Rete pegs contribute to oral epithelial adhesion by enlarging the contact areas, whereas integrins are the major molecules that mediate epithelial cell adhesion to the basement membrane. Keratinocyte growth factor (KGF) can promote both rete peg elongation in the skin and the expression of integrins in various cell types. Herein, we tested the effects of submucosal injection of KGF in the ventral surfaces of rat tongues on oral epithelial adhesion. The data confirmed that topical injection of KGF elevated the adhesive forces, elongated the rete pegs, and increased the abundance of integrins, KGF, and KGF receptor on the rat tongue ventral surface. However, HYD-1 (Lys-Ile-Lys-Met-Val-Ile-Ser-Trp-Lys-Gly), an integrin antagonist, inhibited the KGF-enhanced epithelial adhesion and rete peg elongation. Moreover, KGF promoted the expression of integrin subunits α6, β4, α3, and β1 in human immortalized oral epithelial cells in 2- and 3-dimensional culture systems. In vitro cell attachment assays demonstrated that HYD-1 inhibited the adhesion of human immortalized oral epithelial cells on Matrigel. Strikingly, the expression of integrins, KGF, and KGFR in human masticatory mucosae with longer rete pegs was more abundant than that in the lining mucosae with shorter rete pegs. In addition, rete peg lengths were positively correlated with the expression levels of integrins, KGF, and KGF receptor. These findings indicate that KGF strengthens oral epithelial adhesion and rete peg elongation via integrins.

Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates LPS-Induced Inflammation and Alveolar Remodeling in the Developing Lung.

In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2+/+ and NOX2-/- mice were injected with intraperitoneal LPS to induce sepsis. Lung inflammation and canonical TLR signaling were assessed 24 hours after LPS. Alveolar development was examined in 15-day-old mice after LPS on Day 6. The in vivo efficacy of a NOX2 inhibitor (NOX2-I) on NOX2 complex assembly and sepsis-induced lung inflammation were examined. Lung cytokine expression and neutrophil influx induced with sepsis in NOX2+/+ mice was decreased by >50% in NOX2-/- mice. LPS-induced TLR4 signaling evident by inhibitor of NF-κB kinase-β and mitogen-activated protein kinase phosphorylation, and nuclear factor-κB/AP-1 translocation were attenuated in NOX2-/- mice. LPS increased matrix metalloproteinase 9 while decreasing elastin and keratinocyte growth factor levels in NOX2+/+ mice. An LPS-induced increase in matrix metalloproteinase 9 and decrease in fibroblast growth factor 7 and elastin were not evident in NOX2-/- mice. An LPS-induced reduction in radial alveolar counts and increased mean linear intercepts were attenuated in NOX2-/- mice. LPS-induced NOX2 assembly evident by p67phox/gp91phox coimmunoprecipitation was disrupted with NOX2-I. NOX2-I also mitigated LPS-induced cytokine expression, TLR pathway signaling, and alveolar simplification. In a mouse model of neonatal sepsis, NOX2 regulates proinflammatory TLR signaling and alveolar remodeling induced by a single dose of LPS. Our results provide mechanistic insight into the regulation of sepsis-induced alveolar remodeling in the developing lung.

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid-derived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid-initiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for invivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3-treated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel γ expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-κB by RvD3 and AT-RvD3 was seen invitro and by AT-RvD3 invivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injuredmucosa that accelerated restoration of epithelial barrier and function.

Effects of Lavender Oil on Hair Growth-Relevant Enzyme Activity and Cytokine Expression in C57BL/6 Mice

The purpose of this study was to determine the effects of lavender oil (LO) on hair growth-relevant enzyme activity and cytokine expression in C57BL/6 mice. The experimental animals were divided into the following groups: i) normal (N: saline), ii) vehicle control (VC: jojoba oil), iii) positive control (PC: 3% minoxidil), iv) experimental 1 (E1: 3% LO), and v) experimental 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. At week 4, the activities of γ-glutamyl transpeptidase (GT) in the E1 and E2 groups were 11% and 15% higher than the N group (p<0.05), respectively. The expression levels of keratinocyte growth factor (KGF) mRNA were significantly greater [10%; ( p<0.05)] in the E1 and E2 groups, compared to the N group. The expression of insulin-like growth factor (IGF)-1 mRNA also significantly increased by 21% and 22% (p<0.05) in the E1 and E2 groups, compared to the N group, respectively. Hepatocyte growth factor (HGF) mRNA expression levels were significantly higher in the E1 and E2 groups than the N group [14% and 17%; (p<0.05)], respectively. The expression of vascular endothelial growth factor (VEGF) mRNA increased by 22% (p<0.05) in both the E1 and E2 groups, when compared to the N group. The correlation coefficients among hair growth-relevant factors were significantly high each other (p<0.001). The correlation coefficient between hair growth area and KGF mRNA expression was 0.940. These results confirm that LO has hair growth-promoting effects as identified by hair growth-relevant enzyme activity and cytokine expression in C57BL/6 mice.

Suppression of MicroRNA-219-5p Activates Keratinocyte Growth Factor to Mitigate Severity of Experimental Cirrhosis

Background/Aims: Keratinocyte growth factor (KGF) plays a critical role in prevention of cirrhosis and enhancement of liver regeneration. However, the molecular regulation of KGF in liver is unknown. MicroRNAs (miRNAs) control the pathogenesis of cirrhosis, whereas the exact involved miRNAs and molecular signaling pathways remain ill-defined. Here we addressed these questions. Methods: We examined the correlation of the levels of miR-219-5p and KGF in the liver biopsies from patients with liver diseases. The effects of overexpression or suppression of miR-219-5p on KGF were examined in both human and mouse hepatic stellate cells (HSCs). Bioinformatics analysis was applied to examine the binding of human/mouse miR-219-5p to the 3'-UTR of human/mouse KGF mRNA, respectively. Finally, adeno-associated viruses carrying antisense of miR-219-5p were infused into the liver from the mice that had developed cirrhosis by carbon tetrachloride (CCl₄), and the effects on KGF levels and liver damage and function were examined. Results: The levels of miR-219-5p and KGF in the liver biopsies were inversely correlated. MiR-219-5p inhibited KGF expression in both human and mouse HSCs, through directly binding the 3'-UTR of KGF mRNA. Expression of antisense of miR-219-5p significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl₄. Conclusions: Suppression of miR-219-5p may benefit the liver regeneration and prevent cirrhosis through increasing KGF.

Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by Pseudomonas aeruginosa via Inhibiting Overproduction of Prostaglandin E2.

New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection. The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia. ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2 ) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2 , ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well. In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2 , which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa.

Possible Involvement of Keratinocyte Growth Factor in the Persistence of Hyperpigmentation in both Human Facial Solar Lentigines and Melasma.

Possible Involvement of Keratinocyte Growth Factor in the Persistence of Hyperpigmentation in both Human Facial Solar Lentigines and Melasma.

Clinical significance of keratinocyte growth factor and K-sam gene expression in gastric cancer

Although gastric cancer is increasingly being detected at an early stage of development, diffuse growth-type malignant tumors, such as scirrhous gastric cancer, are usually at an advanced stage at the time of diagnosis, resulting in poor treatment outcomes. The aim of this study was to determine whether the K-sam gene and keratinocyte growth factor (KGF) expression may be used to identify malignant tumors with a poor prognosis. K-sam and KGF expression was retrospectively evaluated in samples from 86 patients with early and advanced gastric cancer according to type, by examining serum levels and using immunohistochemical staining. The associations with clinicopathological characteristics and survival were also examined. The mean serum KGF levels were 11.191±3.808 pg/ml in early stage and 10.715±3.4991 pg/ml in advanced gastric cancer patients. KGF levels were significantly higher in types 4 and 5 (14.498±3.812 pg/ml, n=6) compared with types 1, 2 and 3 (10.747±3.571 pg/ml, n=80; P=0.028). Stage classification was identified as the only significant factor which determined overall survival. Patients with KGF-positive tumors had significantly higher serum KGF levels compared with those who had KGF-negative tumors. Patients with K-sam-positive tumors had significantly higher KGF levels compared with those who had K-sam-negative tumors. Pathological KGF expression was not significantly correlated with the degree of differentiation; however, there was a positive correlation between high K-sam expression in scirrhous gastric tumors and serum KGF levels. The present study revealed that high serum KGF levels are a risk factor for diffuse infiltrative gastric cancer and may provide a simple method of identifying patients with a poor prognosis among previously diagnosed preoperative gastric cancer patients.

An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds

We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds—composed of a blend of the degradable polymers poly(l-lactide) (PLA) or polycaprolactone (PCL)—that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full-thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds.