Expression Of Fibroblast Growth Factor Research Articles

FGF2 Alleviates Microvascular Ischemia-Reperfusion Injury by KLF2-mediated Ferroptosis Inhibition and Antioxidant Responses.

An essential pathogenic element of acute limb ischemia/reperfusion (I/R) injury is microvascular dysfunction. The majority of studies indicates that fibroblast growth factor 2 (FGF2) exhibits protective properties in cases of acute I/R injury. Albeit its specific role in the context of acute limb I/R injury is yet unknown. An impressive post-reperfusion increase in FGF2 expression was seen in a mouse model of hind limb I/R, followed by a decline to baseline levels, suggesting a key role for FGF2 in limb survivability. FGF2 appeared to reduce I/R-induced hypoperfusion, tissue edema, skeletal muscle fiber injury, as well as microvascular endothelial cells (ECs) damage within the limb, according to assessments of limb vitality, Western blotting, and immunofluorescence results. The bioinformatics analysis of RNA-sequencing revealed that ferroptosis played a key role in FGF2-facilitated limb preservation. Pharmacological inhibition of NFE2L2 prevented ECs from being affected by FGF2's anti-oxidative and anti-ferroptosis activities. Additionally, silencing of kruppel-like factor 2 (KLF2) by interfering RNA eliminated the antioxidant and anti-ferroptosis effects of FGF2 on ECs. Further research revealed that the AMPK-HDAC5 signal pathway is the mechanism via which FGF2 regulates KLF2 activity. Data from luciferase assays demonstrated that overexpression of HDAC5 prevented KLF2 from becoming activated by FGF2. Collectively, FGF2 protects microvascular ECs from I/R injury by KLF2-mediated ferroptosis inhibition and antioxidant responses.

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage.

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer's disease mouse models and patients, and that it plays a vital role in the learning and memory. However, the underlying mechanisms of fibroblast growth factor 13 in Alzheimer's disease remain unclear. In this study, we established rat models of Alzheimer's disease by stereotaxic injection of amyloid-β (Aβ1-42)-induced into bilateral hippocampus. We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13. The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer's disease model rats. After overexpression of fibroblast growth factor 13, learning and memory abilities of the Alzheimer's disease model rats were remarkably improved. Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione, superoxide dismutase, phosphatidylinositol-3-kinase, AKT and glycogen synthase kinase 3β, and anti-apoptotic factor BCL. Furthermore, fibroblast growth factor 13 overexpression decreased the number of apoptotic cells, expression of pro-apoptotic factor BAX, cleaved-caspase 3 and amyloid-β expression, and levels of tau phosphorylation, malondialdehyde, reactive oxygen species and acetylcholinesterase in the brain of Alzheimer's disease model rats. The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer's disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3β signaling pathway.

Radix Salvia miltiorrhiza Ameliorates Burn Injuries by Reducing Inflammation and Promoting Wound Healing.

Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats. The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue. RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-β1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney. RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.

Artificial nerve graft constructed by coculture of activated Schwann cells and human hair keratin for repair of peripheral nerve defects.

Studies have shown that human hair keratin (HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.

Dimethyl Fumarate Protects Retinal Pigment Epithelium from Blue Light-Induced Oxidative Damage via the Nrf2 Pathway.

The purpose of this study is to investigate the protective effect of dimethyl fumarate (DMF), the methyl-ester of fumaric acid, against blue-light (BL) exposure in retinal pigment epithelial (RPE) cells. ARPE-19 cells, a human RPE cell line, were cultured with DMF followed by exposure to BL. Reactive oxygen species (ROS) generation, cell viability, and cell death rate were determined. Real-time polymerase chain reaction and Western blotting were performed to determine the change in nuclear factor (erythroid-derived)-like 2 (NRF2) expression. Twenty-seven inflammatory cytokines in the supernatant of culture medium were measured. BL exposure induced ROS generation in ARPE-19 cells, which DMF alleviated in a concentration-dependent manner. BL exposure increased the ARPE-19 cell death rate, which DMF alleviated. BL exposure induced ARPE-19 cell apoptosis, again alleviated by DMF. Under BL exposure, DMF increased the NRF2 mRNA level and promoted NRF2 expression in the nucleus. BL also strongly increased interleukin (IL)-1β and fibroblast growth factor (FGF) expression. BL strongly induced RPE cell damage with apoptotic change while DMF mainly reduced inflammation in BL-induced RPE damage, resulting in blockade of cell death. DMF has a protective effect in RPE cells against BL exposure via activation of the NRF2 pathway.

Potential of Anadara granosa Nanoparticles to improve the Expression of the Fibroblast Growth Factor-2 (FGF-2) in Chronic wound of Hyperglycemia conditions

Background: Hyperglycemia can cause adverse effects in the oral cavity, one of which is inhibiting wound healing. Chronic hyperglycemia reduces the expression and distribution of growth factors, such as fibroblast growth factor-2 (FGF-2), a significant growth factor in angiogenesis. The disruption of wound healing may lead to chronic wounds to further infection. Routine oral wound treatment using topical steroid ointment is considered ineffective in hyperglycemic individuals due to its anti-angiogenic properties. Anadara granosa shell nanoparticles can induce the production of numerous growth factors such as FGF-2 and augment angiogenesis. Objective: To determine the potential of giving Anadara granosa shell nanoparticles to increase FGF-2 in chronic inflammatory wounds with hyperglycemia conditions. Discussion: Angiogenesis supports and intersects with other ongoing proliferative activities and with the remodeling phase. FGF-2 helps the proliferation of endothelial cells and the arrangement of endothelial cells to form a tube to help angiogenesis. Hyperglycemia is directly associated with a significant reduction in FGF-2-induced angiogenesis in vivo. Biogenic CaCO3 nanoparticles made from Anadara granosa have shown promising potential to increase FGF-2 by activating NF-κB signaling. Conclusion: Anadara granosa shell nanoparticles have the potential to increase the expression of fibroblast growth factor-2 (FGF-2) in chronic inflammatory wounds with hyperglycemia conditions.

Sex difference on fibroblast growth factors (FGFs) expression in skin and wound of streptozotocin(STZ)-induced type 1 diabetic mice.

Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family's expression patterns in skin and wounds influenced by both diabetes and sex are still unknown. In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family's expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgfexpressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) - a FGFR activation marker gene - in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury). Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.

Potato Alkaloids α-Solanine and α-Chaconine Promote bFGF and VEGF Expression in Vein and Adjacent Tissues in the Rabbit Model of Phlebitis

Objectives: To investigate the therapeutic effect of mashed potato and its alkaloids α-solanine and α-chaconine on basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression in ear venous vessels and adjacent tissues in a rabbit model of phlebitis. Materials and Methods: Japanese white rabbits were randomly allocated into control, vaseline cream (model), magnesium sulfate, mashed potato, α-solanine cream 100 mg/kg or 200 mg/kg, and α-chaconine cream 100 mg/kg or 200 mg/kg groups. The phlebitis model was established by intravenous infusion of vincristine in the rabbit ears. Group A received physiological saline. Group B−F was applied treatment 3 times/day, for 2 days along the ears vein. The alkaloid contents in α-solanine and α-chaconine were analyzed with HPLC. The bFGF, protein kinase C alpha (PKC-α), and VEGF expression in the ear vessels and nearby tissues were analyzed using immunohistochemistry, polymerase chain reaction (PCR), and Western blot analysis, respectively. Results: After phlebitis modeling, the vascular endothelium of the rabbit ear vein was damaged or layered, the lumen was swollen and deformed to an oval or round shape, and the proportion of bFGF and VEGF positive areas in the vascular endothelium and adjacent tissues was higher than the control group. The phlebitis score shows that various treatments have certain effects, among which magnesium sulfate wet gauze and mashed potatoes are more effective. The application of α-solanine and α-chaconine cream promotes the expression of bFGF and VEGF, as well as PKC-α in the venous blood vessels and adjacent tissues, but mashed potatoes had little effect. Conclusion: α-solanine and α-chaconine cream can promote the expression of bFGF and VEGF in venous blood vessels and adjacent tissues, which may contribute to the recovery of blood vessels in phlebitis.

DNA damage to bone marrow stromal cells by antileukemia drugs induces chemoresistance in acute myeloid leukemia via paracrine FGF10–FGFR2 signaling

Chemo-resistance remains a major challenge in the current treatment of acute myeloid leukemia (AML). The bone marrow microenvironment (BMM) plays a complex role in protecting leukemia cells from chemotherapeutics, and the mechanisms involved are not fully understood. Anti-leukemia drugs kill AML cells directly but also damage the BMM. Here, we determined anti-leukemia drugs induce DNA damage in bone marrow stromal cells (BMSCs), resulting in resistance of AML cell lines to adriamycin and idarubicin killing. Damaged BMSCs induced an inflammatory microenvironment through NF-κB; suppressing NF-κB with small molecule inhibitor Bay11-7082 attenuated the pro-survival effects of BMSCs on AML cell lines. Furthermore, we used an ex vivo functional screen of 507 chemokines and cytokines to identify 44 proteins secreted from damaged BMSCs. Fibroblast growth factor-10 (FGF10) was most strongly associated with chemo-resistance in AML cell lines. Additionally, expression of FGF10 and its receptors, FGFR1 and FGFR2, was increased in AML patients after chemotherapy. FGFR1 and FGFR2 were also widely expressed by AML cell lines. FGF10-induced FGFR2 activation in AML cell lines operates by increasing P38 MAPK, AKT, ERK1/2, and STAT3 phosphorylation. FGFR2 inhibition with small molecules, or gene silencing of FGFR2 inhibited proliferation and reverses drug-resistance of AML cells by inhibiting P38 MAPK, AKT, and ERK1/2 signaling pathways. Finally, release of FGF10 was mediated by β-catenin signaling in damaged BMSCs. Our data indicate FGF10-FGFR2 signaling acts as an effector of damaged BMSC-mediated chemo-resistance in AML cells, and FGFR2 inhibition can reverse stromal protection and AML cell chemo-resistance in the BMM.

An Exploratory In Vivo Study on the Effect of Annurca Apple Extract on Hair Growth in Mice.

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of AAE by orally administering AAE in six-week-old C57BL/6 mice once a day for 21 d. We observed improvement in hair length, thickness, weight, and density. The gene expression of two growth factors related to hair growth, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 7 (FGF-7), were measured using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene expression of both VEGFA and FGF-7 increased significantly in the AAE-treated group. Additionally, treatment with AAE suppressed the gene expression of type 1 5α-reductase. Histological analysis showed that protein levels of cytokeratin 5 and 10 were increased in the skin tissues of the AAE-treated group. These results suggest that AAE might be a potential therapeutic natural product that prevents hair loss by promoting the expression of hair growth-related factors.

Expression of the neuroprotective factors BDNF, CNTF, and FGF-2 in normal and oxygen induced retinopathy.

Oxygen-induced retinopathy is a type of retinal pathological neovascularization (NV) disease that leads to vision loss and translates to a significant societal cost. Anti-vascular endothelial growth factor (VEGF) and anti-inflammatory treatments have been widely used in the clinic, but the results have not been entirely satisfactory. It is necessary to explore other treatments for Ischemic retinal diseases. The oxygen-induced retinopathy (OIR) model was induced from P7 to P12 as described. Histology evaluation (HE) and retina flat mounts were checked at P17 to confirm the establishment of the OIR model. Retinal ganglion cell (RGC) degeneration was checked by transmission electron microscopy at P17 to confirm the neurological damage caused by OIR. Western blot analysis was performed at P12, P15, and P17 to study the expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and fibroblast growth factor 2 (FGF-2) in normal and OIR mice. Comparative analysis of the expressions of BDNF, CNTF, and FGF-2 in normal and OIR mice was performed. There were many retinal NV and non-perfusion areas in OIR P17. RGCs were degenerated at OIR P17. The expressions of BDNF, CNTF, and FGF-2 gradually increased from P12 to P17 in normal mice and were much higher in OIR mice. The expression curves of BDNF, CNTF, and FGF-2 in the OIR model were inconsistent and did not correlate with each other. This study provides evidence for changes in BDNF, CNTF, and FGF-2 in Oxygen-induced retinopathy.

Secretome of hypoxia-preconditioned mesenchymal stem cells enhance the expression of HIF-1a and bFGF in a rotator cuff tear model.

Aim To determine the effect of secretome hypoxia mesenchymal stem cells (SH-MSCs) on the relative gene expression of hypoxia inducible factor-1a (HIF-1a) and basic fibroblast growth factor (bFGF) in accelerating histomorphometric repair of tendon to bone interface healing in rats acute rotator cuff tear (RCT) model. Methods This is experimental research with posttest control group design. Thirty-male Wistar rats were divided into five treatment groups: healthy group and rotator cuff reconstruction group included four groups: SH-MSCs W2 (the treatment group was given a SH-MSCs 0.5 mL and terminated at weeks 2), NaCl W2 (the control vehicle group was given NaCl 0.5 mL and terminated at weeks 2), SH-MSCs W8 (the treatment group was given a SH-MSCs 0.5 mL and terminated at weeks 8), and NaCl W8 (the control vehicle group was given NaCl 0.5 mL and terminated at weeks 8). On the termination day, all the rats were terminated and HIF-1a and bFGF gene expression were analysed using qRT-PCR. Results SH-MSCs significantly increased the HIF-1a and bFGF gene expression than NaCl group even in week 2 and week 8. The highest increased gene expression of HIF-1a and bFGF was on week 8. Conclusion SH-MSCs are important in the healing repair process of tendon-to-bone interface in acute RCT model rats through increasing gene expression of HIF-1α and bFGF.

Blockade of FGF2/FGFR2 Partially Overcomes Bone Marrow Mesenchymal Stromal Cells Mediated Progression of T-Cell Acute Lymphoblastic Leukaemia

The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the protection effects of abnormal bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to investigate MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukemic niche formation. RNA sequence results revealed that T-ALL derived MSCs secreted fibroblast growth factor 2 (FGF2), which combined with fibroblast growth factor receptor 2 (FGFR2) on leukaemia cells, resulting in activation of PI3K/AKT/mTOR signalling in leukaemia cells. In vitro blocking the interaction between FGF2 and FGFR2 with infigratinib (BGJ398), a FGFR1-3 kinase inhibitor, or knockdown FGF2 expression in MSCs in co-culture system, both induced deactivation of PI3K/AKT/mTOR signalling pathway in T-ALL cells and dysregulations of genes associated with cell cycle and apoptosis, leading to decrease of leukaemia cells. In mouse model with FGF2 and FGFR2 blockade, overall survival was extended and dissemination of leukaemia cells in BM, spleen, liver and peripheral blood was decreased. After subcutaneous injection of primary human T-ALL cells with MSCs, tumour growth was suppressed when FGF2/FGFR2 was interrupted. Thus, inhibition of FGF2/FGFR2 interaction appears to be a valid strategy to overcome BM-MSCs mediated progression of T-ALL, and infigratinib could indeed improve outcomes in T-ALL, which provide theoretical basis of infigratinib as a therapeutic strategy to control disease progression.

Curcumin improves insulin sensitivity in high-fat diet-fed mice through gut microbiota

BackgroundInsulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice.MethodsGlucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100 mg kg−1 d−1, p.o.) or vehicle for 4 weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4 weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).ResultsCurcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota.ConclusionsThe effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.

Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus.

Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.

The effects of mesenchymal stromal cells and platelet-rich plasma treatments on cutaneous wound healing.

Cellular therapy and platelet-rich plasma (PRP) have been used as a treatment for skin wounds. Previous evidence has shown that mesenchymal stromal cells (MSC) may improve skin wound healing. In contrast, contradictory effects have been reported by using PRP treatment on skin wound healing. However, there is evidence that PRP constitutes an excellent scaffold for tissue engineering. In this work, we aim to study the effect of MSC on skin wound healing. We used an experimental murine model of full-thickness wounds. Wounds were treated with human bone marrow-MSC contained in a PRP clot. Untreated or PRP-treated wounds were used as controls. Wound healing was evaluated by macroscopic observation and histological analysis at day 7 post-wounding. Immunohistochemical studies were performed to detect the presence of epithelial progenitor cells (EPC) and the expression of basic fibroblast growth factor (bFGF). MSC/PRP implantation induced a significant wound closure and re-epithelialization as compared with the controls. Increase of CD34+ cells and bFGF was observed in the wounds treated with MSC/PRP. Our results show that MSC included in PRP clot induce cutaneous wound repair by promoting re-epithelialization, migration of EPC and expression of bFGF. PRP alone does not exert a significant effect on wound healing. Our results support the possible clinical use of MSC in PRP scaffold as potential treatment of skin wounds.

El efecto del scaffold de hidroxiapatita derivada de Portunus pelagicus sobre la expresión del factor de crecimiento de fibroblastos-2 (FGF-2) y las proteínas morfogenéticas óseas-2 (BMP-2) en los alvéolos dentarios de Cavia cobaya

Objetive: To determine the expression of Fibroblast Growth Factor (FGF)-2 and Bone Morphogenetic Protein (BMP)-2 after application of scaffold hydroxyapatite from Rajungan crab shell (Portunus pelagicus) in the tooth extraction socket of Cavia cobaya. Material and Methods: This study used a post-test only control group design with 28 Cavia cobaya separated into two groups, control and treatment group. The left mandibular incisor was extracted, and socket preservation was conducted. A hydroxyapatite graft derived from crab shells was mixed with gelatin and eventually turned into a scaffold, which was afterward put into the extraction socket. After 7 days and 14 days, each group was terminated and examined using immunohistochemical staining to observe the expression of FGF-2 and BMP-2. One-Way Anova and Tukey HSD were used to examine the research data. Results: FGF-2 and BMP-2 expressions were observed higher in the group that received hydroxyapatite scaffold at the post-extraction socket than those in the group that did not receive hydroxyapatite scaffold. Conclusion: The application of a hydroxyapatite scaffold from Rajungan crab shell (Portunus pelagicus) to the tooth extraction socket can increase FGF-2 and BMP-2 expression.

Phosphorylation of RXRα mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome

The cJun NH2-terminal kinase (JNK) signaling pathway in the liver promotes systemic changes in metabolism by regulating peroxisome proliferator-activated receptor α (PPARα)-dependent expression of the hepatokine fibroblast growth factor 21 (FGF21). Hepatocyte-specific gene ablation studies demonstrated that the Mapk9 gene (encoding JNK2) plays a key mechanistic role. Mutually exclusive inclusion of exons 7a and 7b yields expression of the isoforms JNK2α and JNK2β. Here we demonstrate that Fgf21 gene expression and metabolic regulation are primarily regulated by the JNK2α isoform. To identify relevant substrates of JNK2α, we performed a quantitative phosphoproteomic study of livers isolated from control mice, mice with JNK deficiency in hepatocytes, and mice that express only JNK2α or JNK2β in hepatocytes. We identified the JNK substrate retinoid X receptor α (RXRα) as a protein that exhibited JNK2α-promoted phosphorylation invivo. RXRα functions as a heterodimeric partner of PPARα and may therefore mediate the effects of JNK2α signaling on Fgf21 expression. To test this hypothesis, we established mice with hepatocyte-specific expression of wild-type or mutated RXRα proteins. We found that the RXRα phosphorylation site Ser260 was required for suppression of Fgf21 gene expression. Collectively, these data establish a JNK-mediated signaling pathway that regulates hepatic Fgf21 expression.

Systematic analysis of expression profiles and prognostic significance of the FGF gene family in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with one of the highest associated mortality rates worldwide, and a 5-year survival rate of <5%. Fibroblast growth factors (FGFs) serve important roles in numerous cellular functions, and dysregulation of FGFs contributes to various cancer types. However, there are few reports on the function of FGFs in PAAD. The Assistant for Clinical Bioinformatics database, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter and Tumor Immune Estimation Resource were utilized to perform the protein-protein interaction network, functional enrichment, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox, differential expression, prognostic value and immune cell infiltration analyses of FGFs in patients with PAAD. Immunohistochemistry (IHC) was used to verify the predictive value of the model. A total of 22 FGF genes were identified. Based on the results of LASSO Cox regression analysis, a total of six genes, including FGF2, FGF8, FGF9, FGF13, FGF17 and FGF22, were selected for the establishment of the prognostic gene signature. High transcriptional levels of FGF17 and FGF22 were significantly associated with long overall survival. The expression of FGFs was associated with the infiltration of various immune cells. According to univariate and multivariate analyses, FGF2 and FGF8 may be useful independent prognostic biomarkers for the prognosis of patients with PAAD. IHC demonstrated that FGF2 and FGF8 were more highly expressed in PAAD tissues compared with that in normal tissues. The present findings offer a novel understanding for the selection of FGF prognostic biomarkers in PAAD.

Silencing of long non-coding RNA TUC338 inhibits the malignant phenotype of nasopharyngeal cancer cells via modulating the miR-1226-3p/FGF2 axis

Long noncoding RNAs (lncRNAs) have been suggested as essential regulators in the cancer progression. LncRNA TUC338 was found to promote the malignancy of various cancers, however, the involvement of TUC338 in nasopharyngeal cancer (NPC) has not been well characterized. Here, our results found the significant overexpression of TUC338 in NPC tissues. Higher level of TUC338 was also observed in NPC cells. Interestingly, NPC patients harboring overexpressed TUC338 have worse prognosis. Functional study indicated that down-regulated TUC338 remarkably suppressed the NPC cell proliferation and cell migration. Notably, depletion of TUC338 significantly inhibited the in vivo tumor growth. Mechanistically, TUC338 acted as molecular sponge of miR-1226-3p and attenuated the negative regulation of miR-1226-3p on the expression of fibroblast growth factor 2 (FGF2). Down-regulation of TUC338 inhibited FGF2 expression in NPC cells and tumor tissues. Overexpression of FGF2 attenuated the suppressed NPC proliferation upon the depletion of TUC338. Our results demonstrated the novel function of TUC338/miR-1226-3p/FGF2 axis in NPC progression, suggesting the potential diagnosis and therapeutics significance of TUC338 in NPC.