Matrix Metalloproteinase-1 Expression Research Articles

Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.

Regulation of Cell Viability, p53 Promoter Activity, and Expression of Interleukin-8, Matrixmetalloproteinase-1 and Tissue Inhibitor of Matrixmetalloproteinase-1 in Non-Irradiated or UV-Irradiated Fibroblasts and Melanoma Cells

Regulation of Cell Viability, p53 Promoter Activity, and Expression of Interleukin-8, Matrixmetalloproteinase-1 and Tissue Inhibitor of Matrixmetalloproteinase-1 in Non-Irradiated or UV-Irradiated Fibroblasts and Melanoma Cells

Protective effects of alpinetin against interleukin-1β-exposed nucleus pulposus cells: Involvement of the TLR4/MyD88 pathway in a cellular model of intervertebral disc degeneration

Intervertebral disc degeneration (IDD) causes a variety of symptoms such as low back pain, disc herniation, and spinal stenosis, which can lead to high social and economic costs. Alpinetin has an anti-inflammatory potential, but its effect on IDD is unclear. Herein, we investigated the effect of alpinetin on IDD. To mimic an in vitro model of IDD, nucleus pulposus cells (NPCs) were exposed to interleukin 1β (IL-1β). The viability of NPCs was assessed by CCK-8 assay. The expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), aggrecan, collagen-2, and matrix metalloproteinase-3 (MMP-3) was examined by qRT-PCR and western blotting. The protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated protein X (Bax), and cleaved caspase-3 were scrutinized by western blotting. The flow cytometry assay was performed to assess apoptosis of NPCs. The contents of inflammatory factors were examined by ELISA kits. Results showed that alpinetin repressed IL-1β-tempted activation of the TLR4/MyD88 pathway and apoptosis in NPCs. Alpinetin alleviated IL-1β-tempted inflammatory responses and oxidative stress in NPCs. Moreover, alpinetin lessened IL-1β-tempted extracellular matrix (ECM) degeneration in NPCs by enhancing the expression of aggrecan and collagen-2 and reducing the expression of MMP-3. The effects of alpinetin on IL-1β-exposed NPCs were neutralized by TLR4 upregulation. In conclusion, alpinetin repressed IL-1β-tempted apoptosis, inflammatory responses, oxidative stress, and ECM degradation in NPCs through the inactivation of the TLR4/MyD88 pathway.

Effect of Human Platelet-Rich Fibrin Lysate on Collagen Type I, Collagen Type III, and Matrix Metalloproteinase 1 : A Protocol Study on Rat Models with Pelvic Organ Prolapse

Background Pelvic organ prolapse (POP) is a prevalent condition caused by weakened pelvic floor support structures. Extracellular matrix alterations, including changes in collagen type I, collagen type III, and matrix metalloproteinase 1 (MMP-1), contribute to the pathogenesis of this condition. Human platelet-rich fibrin lysate (hPRF-L) is a novel regenerative treatment that has shown beneficial results in treating structural weaknesses related to various pelvic floor diseases, including POP. Methods This study protocol aims to investigate the effects of hPRF-L injection on collagen I, III, and MMP-1 in the vaginal mucosa of a rat POP model. POP will be induced in female Sprague-Dawley rats, which will be randomly assigned to control, sham, and hPRF-L treatment groups. The hPRF-L group will receive weekly injections of hPRF-L (25, 50, or 75 μL) into the vaginal mucosa for 4 weeks. Vaginal tissue samples will be collected, and collagen type I, collagen type III, and MMP-1 expression will be evaluated using quantitative reverse transcription polymerase chain reaction and immunohistochemical analyses. Data analysis will be performed with ANOVA and post-hoc tests. Discussion The findings from this study protocol are expected to provide valuable insights into the mechanisms by which hPRF-L impacts the structural integrity of the pelvic floor. By elucidating these mechanisms, this study aims to inform future POP treatment strategies. The anticipated results are an increase in collagen type I and III expression and a reduction in MMP-1 levels in the hPRF-L treatment group compared to the control and sham groups. These outcomes could support the use of hPRF-L as a regenerative therapy for managing POP, offering a potential alternative to more invasive surgical interventions. Conclusion The expected results will contribute to the development of less invasive treatments for POP, improving patient outcomes and quality of life.

Effects of electroacupuncture at "Jiaji" (EX-B 2) on extracellular matrix of chondrocytes and inflammatory reaction in rabbits with Modic changes of cartilage endplate

To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) on extracellular matrix (ECM) of chondrocytes and inflammatory reaction in rabbits with Modic changes (MC) of cartilage endplate, and to explore the mechanism of EA in treating MC of endplate cartilage. Eighteen male New Zealand white rabbits were randomly divided into a sham operation group, a model group and an EA group, 6 rabbits in each group. Based on the autoimmune theory, MC model was established by embedding autogenous nucleus pulposus in the rabbits of the model group and the EA group, based on autoimmunity. After successful modeling, EA was applied at bilateral "Jiaji" (EX-B 2) of L5 and L6 in the EA group, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, 20 min a time, once a day, 1-day interval was taken after continuous 6-day intervention, for 4 weeks totally. Before and after modeling, as well as before and after intervention, the comprehensive response score was observed. After modeling and intervention, magnetic resonance imaging (MRI) was used to observe the signal intensity of intervertebral disc and cartilage endplate. After intervention, the morphology of chondrocytes of cartilage endplate was observed by HE staining; the positive expression of a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS5) and Aggrecan in the cartilage endplate was detected by immunohistochemistry; the levels of inflammatory factors i.e. interleukin-1β (1L-1β) and tumor necrosis factor-α (TNF-α) in the cartilage endplate were detected by ELISA; the protein expression of ADAMTS5, Aggrecan, matrix metalloproteinase-13 (MMP-13), IL-1β and TNF-α in the cartilage endplate was detected by Western blot. Compared with the sham operation group, in the model group, the comprehensive response score was decreased (P<0.01); L5/L6 intervertebral disc and the cancellous bones of endplate vertebral body showed low signal and unclear boundary; the chondrocytes of the cartilage endplate increased significantly, the cells were enlarged and hypertrophic, and the nuclei were wrinkled and clustered; the positive expression of ADAMTS5 as well as the levels of IL-1β and TNF-α were increased (P<0.01), while the positive expression of Aggrecan was decreased (P<0.01) in the cartilage endplate; the protein expression of ADAMTS5, MMP-13, IL-1β and TNF-α was increased (P<0.01), while that of Aggrecan was decreased (P<0.01) in the cartilage endplate. Compared with the model group, in the EA group, the comprehensive response score was increased (P<0.01); the signal of L5/L6 intervertebral disc and the cancellous bones of endplate vertebral body was enhanced; the chondrocytes of the cartilage endplate were reduced, the nuclei were slightly crumpled and scattered; the positive expression of ADAMTS5 as well as the levels of IL-1β and TNF-α were decreased (P<0.05, P<0.01), while the positive expression of Aggrecan was increased (P<0.01) in the cartilage endplate; the protein expression of ADAMTS5, MMP-13, IL-1β and TNF-α was decreased (P<0.05, P<0.01), while that of Aggrecan was increased (P<0.05) in the cartilage endplate. EA at "Jiaji" (EX-B 2) can delay the MC of cartilage endplate. The mechanism may be related to inhibiting the degradation of ECM of chondrocytes and the secretion of inflammatory factors, and repairing the degeneration of endplate cartilage.

Protective effect of ferulic acid-hyaluronic acid copolymer against UVB irradiation in a human HaCaT cell line

Excessive UVB exposure increased the production of reactive oxygen species (ROS), leading to oxidative damage and epidermal inflammation. To enhance UVB protection effect, a strong phenolic antioxidant, ferulic acid (FA) was designed onto HA via a free radical mediated method. Our previous work has confirmed its structural characterization and in vitro antioxidant. The aim of this study was to evaluate its protective effects against UVB-induced damage in human HaCaT cells. We observed a significant reduction in cell viability to 57.43 % following UVB exposure at a dose of 80 mJ/cm2. However, pretreatment with FA-HA (250 to 2000 μg·mL−1) significantly attenuated cytotoxicity in a dose-dependent manner. Furthermore, FA-HA was found to suppress the intracellular generation of ROS and up-regulated the expression of the antioxidant enzyme superoxide dismutase (SOD). The elevated levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as well as the mRNA expression of matrix metalloproteinase-1/9 (MMP-1/9) induced by UVB irradiation, were also effectively reduced by FA-HA. Additionally, FA-HA treatment decreases the phosphorylation of mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1), ultimately preventing apoptosis. These findings suggest that FA-HA is a promising candidate for UVB protection in skincare formulations.

Chikusetsusaponin IVa from Dolichos lablab Linne attenuates UVB-induced skin photoaging in mice by suppressing MAPK/AP-1 signaling

Ultraviolet-B (UVB) radiation-induced photoaging of the skin is characterized by amplified expression of matrix metalloproteinase-1 (MMP-1) and reduced collagen fibers, both of which contribute to skin wrinkle formation. Edible natural products can protect against skin photoaging. Here, we investigate the protective effect of Dolichos lablab Linne (DLL) water extract against UVB radiation-prompted skin damage and attempt to uncover its fundamental mechanisms in human keratinocytes (HaCaT) and HR-1 hairless mouse. We found DLL extract rescued the reduction in cell viability associated with UVB exposure without any associated cytotoxic effects. It also protected against skin photoaging by inhibiting mitogen-activating protein kinase (MAPK) signaling, thereby preventing the UVB-associated increase in MMP-1 and -9 expression. DLL extract also increased the expression of both superoxide dismutase 1 (SOD1) and catalase (CAT). We identified chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A as bioactive components of DLL. Although we have not yet identified the mechanisms by which these compounds reduce the effects of photoaging, we have demonstrated that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce MMP-1, MMP-9, p–c-Fos, and p–c-Jun expression, while also avoiding any cytotoxicity. We found oral administration of DLL extract effectively alleviated dorsal epidermal thickening and skin dehydration in HR-1 hairless mouse visible to UVB. DLL extract also prevents UVB-induced activation of the MAPK/AP-1 signaling pathway, thereby reducing the expression of MMPs in dorsal mouse skin. Our results indicate that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A are bioavailable components of DLL extract that can reduce UVB-induced skin damage via MMPs by deactivating the MAPK/AP-1 signaling pathway. These findings suggest DLL extract can be used as a skin anti-photoaging agent.

Downregulation of carnitine acetyltransferase by promoter hypermethylation regulates ultraviolet-induced matrix metalloproteinase-1 expression in human dermal fibroblasts

BackgroundOverexposure to ultraviolet (UV) radiation accelerates skin aging, resulting in wrinkle formation, reduced skin elasticity, and hyperpigmentation. UV irradiation induces increased matrix metalloproteinases (MMPs) that degrade collagen in the extracellular matrix. Skin aging is also accompanied by epigenetic alterations such as promoter methylation by DNA methyltransferases, leading to the activation or suppression of gene expression. Although carnitine acetyltransferase (CRAT) is implicated in aging, the effect of UV on the expression of CRAT and regulatory mechanisms of UV-induced MMP-1 expression remain unknown. ObjectiveWe investigated changes in CRAT expression upon UV irradiation and its effect on MMP-1 expression. MethodsPrimary human dermal fibroblasts were UV irradiated with either control or 5-AZA-dC. CRAT knockdown or overexpression was performed to investigate its effect on MMP-1 expression. The mRNA level was analyzed by quantitative real-time PCR, and protein level by western blotting. ResultsThe expression of CRAT was decreased in UV-irradiated human skin in vivo and in human dermal fibroblasts in vitro. CRAT was downregulated upon UV irradiation by hypermethylation, and treatment with 5-Aza-2′-deoxycytidine, a DNA methyltransferase inhibitor, reversed UV-induced downregulation of CRAT. CRAT knockdown activated the JNK, ERK, and p38 MAPK signaling pathways, which increased MMP-1 expression. Stable overexpression of CRAT alleviated UV-induced MMP-1 induction. ConclusionCRAT downregulation caused by promoter hypermethylation may play an important role in UV-induced skin aging via upregulation of MMP-1 expression.

The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells.

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.

Elucidation of the anti-colorectal cancer mechanism of Atractylodes lancea by network pharmacology and experimental verification.

Atractylodes lancea which was listed in "Shennong's Materia Medica" and could be used to treat gastrointestinal-associated diseases. However, its roles, core and active ingredients, and mechanisms in treatment of colorectal cancer (CRC) were still unknown. Therefore, network pharmacology and experimental validation were used to clarify the effects, core active ingredients and molecular mechanisms of Atractylodes lancea. We found that Atractylodes lancea has 28 effective active components and 213 potential targets. Seventy-three genes which demonstrate interaction between the Atractylodes lancea and CRC were confirmed. Enrichment analysis showed that 2033 GO biological process items and 144 KEGG pathways. Survival and molecular docking analysis revealed that luteolin as the core component interacted with these genes (Matrix metalloproteinase 3 (MMP3), Matrix metalloproteinase 9 (MMP9), Tissue inhibitor of metalloproteinases 1 (TIMP1), Vascular endothelial growth factor A (VEGFA)) with the lowest binding energy, and these genes were involved in building a prognostic model for CRC. Cellular phenotyping experiments showed that luteolin could inhibit the proliferation and migration of CRC cells and downregulate the expression of MMP3, MMP9, TIMP1, VEGFA probably by Phosphoinositide 3-kinase/ serine/threonine kinase Akt (PI3K/AKT) pathway. To conclude, Atractylodes lancea could inhibit proliferation and migration of CRC cells through its core active ingredient (luteolin) to suppress the expression of MMP3, MMP9, TIMP1, VEGFA probably by PI3K/AKT pathway.

Evaluation of anti-aging and antioxidant properties of a new rose variety, Ever-rose

BackgroundRose flowers contain active ingredients such as flavonoids and volatile oils and are acknowledged to be good natural resources owing to their anti-aging and antioxidant properties. In this study, we develop four new rose varieties (named Ever-rose) that are fragrant, pest resistant, and easy to grow. Subsequently, we evaluate the properties of Ever-rose and its potential for use in anti-aging products.MethodsThe chemical composition of Ever-rose was determined using ultra-high-performance liquid chromatography triple time-of-flight mass spectrometry/mass spectrometry. The antioxidant activity of the Ever-rose extract was evaluated using various assays, including superoxide dismutase activity, 2,2-diphenyl-1-picrylhydrazyl radical-scavenging capacity, and xanthine oxidase activity. The variations in proteolytic matrix metalloproteinase-1 expression, collagen content after ultraviolet (UV) irradiation, and reactive-oxygen-species (ROS) levels after infrared A (IRA) treatment were evaluated. The variations in cell elasticity were assessed via atomic force microscopy.ResultsThe petal extracts of Ever-rose (named ER004(P), ER011(P), ER012(P), and ER015(P)) showed good antioxidant activity. They effectively inhibited UV irradiation-induced MMP-1 expression and IRA irradiation-induced increase in mitochondrial ROS levels. Additionally, they inhibited variations in cell shape and elasticity as aging progressed. In particular, ER011(P) demonstrated the best anti-aging and antioxidant effects.ConclusionThe newly developed Ever-rose showed excellent antioxidant and anti-aging effects. In particular, ER011(P) demonstrated the best properties owing to its high antioxidant content. Hence, it exhibits significant potential as a functional cosmetic ingredient.Graphical

Expression of Matrix Metalloproteinase-3 in the Aqueous Humor of Patients with Posner-Schlossman Syndrome

Purpose To explore the expression of matrix metalloproteinase-3 (MMP-3) in the aqueous humor of patients with Posner-Schlossman syndrome (PSS), and the association between MMP-3 and PSS. Methods Peripheral blood and aqueous humor were routinely collected from 29 patients with PSS (PSS group) and 30 patients with age-related-cataract (ARC) (control group). The content of MMP-3 in serum and aqueous humor was measured by immunoturbidimetry. The correlation between MMP-3 and ophthalmic examination results were verified by Spearman’s correlation analysis. Results The MMP-3 level in the aqueous humor of the PSS group was (25.86 ± 13.4)ng/ml, significantly higher than that in the control group (3.9 ± 2.7)ng/ml(p < 0.001), while there was no significant difference in serum MMP-3 level between the two groups (p = 0.125). The endothelial cell density (ECD) in the aqueous humor of the PSS group was (2078 ± 440) cell/mm2, intraocular pressure (IOP) in the aqueous humor of the PSS group was (33 ± 12) mmHg. The correlation analysis of aqueous humor MMP-3 and various ophthalmic examination results showed that aqueous humor MMP-3 had a moderate correlation with IOP and the difference in ECD between the affected eye and the fellow eye. Conclusions MMP-3 level is elevated in the aqueous humor of PSS patients, and it may play an important role in the pathogenesis of PSS.

Potential skin anti-aging effects of main phenolic compounds, tremulacin and tremuloidin from Salix chaenomeloides leaves on TNF-α-stimulated human dermal fibroblasts

The genus Salix spp. has long been recognized as a healing herb for its use in treating fever, inflammation, and pain relief, as well as a food source for its nutritional value. In this study, we aimed to explore the potential bioactive natural products in the leaves of Salix chaenomeloides, commonly known as Korean pussy willow, for their protective effects against skin damage, including aging. Utilizing LC/MS-guided chemical analysis of the ethanol extract of S. chaenomeloides leaves, with a focus on major compounds, we successfully isolated two main phenolic compounds, tremulacin (1) and tremuloidin (2). Subsequently, we investigated the protective effects of tremulacin (1) and tremuloidin (2) in TNF-α-stimulated human dermal fibroblasts (HDFs). The results revealed that both tremulacin (1) and tremuloidin (2) inhibited TNF-α-stimulation-induced ROS, suppressed matrix metalloproteinase-1 (MMP-1) expression, and enhanced collagen secretion. This implies that both tremulacin (1) and tremuloidin (2) hold promise as preventive agents against photoaging-induced skin aging. Furthermore, we assessed the activity of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and heme oxygenase 1 (HO-1) to elucidate the mechanism of photoaging inhibition by tremuloidin (2), which exhibited superior efficacy. We found that tremuloidin (2) inhibited ERK and p38 phosphorylation and notably suppressed COX-2 expression while significantly upregulating HO-1 expression. These findings suggest potent anti-inflammatory and antioxidant properties of tremuloidin (2), positioning it as a potential candidate for combating photoaging-induced skin aging.

The effect of curcumin 1% methanolic extract on the expression of Matrix Metalloproteinase-1, Matrix Metalloproteinase-8, Matrix Metalloproteinase-13, neutrophil, macrophage, lymphocyte counts in Porphyromonas gingivalis induced periodontitis: a randomized controlled trial

ObjectiveHailed as one of the most fundamental and important treatment in management of periodontal disease, scalling and root planning has limitations regarding microorganism elimination. Meanwhile, turmeric has been proven to have a therapeutic effect on gingivitis and periodontitis. This study aimed to analyze the impact of curcumin 1% methanolic extract on the expression of Matrix Metalloproteinase-1, Matrix Metalloproteinase-8, Matrix Metalloproteinase -13, neutrophil, macrophage, and lymphocyte number in the gingiva of Wistar rats exposed to Porphyromonas gingivalis bacteria (P. gingivalis). Materials and methodsThe experimental animals used were Wistar rats, arbitrarilly split up into three experimental groups namely: normal, control (induced with periodontitis, received no treatment), and treatment (Periodontitis with 1% curcumin treatment). The samples were taken from the gingival tissue of the mandibular incisors on 1 and 7 days. Immunohistochemical and Hematoxylin Eosin staining were performed to measure the expression of Matrix Metalloproteinase-1, Matrix Metalloproteinase-8, Matrix Metalloproteinase-13, and the number of neutrophils, macrophages, and lymphocytes. Data were analyzed for mean standard deviation. The Oneway ANOVA was then performed to see whether there is a significant difference between experimental groups, the test then commenced with Tukey’s Honestly Significant Difference test with a significance level (α=0.05). ResultsMMP-8, MMP-13, neutrophil, and lymphocyte numbers in the treatment groups were significantly lower with P<0.05 than in the control groups in the 1 and 7 days. Meanwhile, in MMP-1 and macrophage numbers the difference was deemed not significant when control and treatment groups are compared. ConclusionThe administration of 1% curcumin can significantly reduce the expression of MMP-8, MMP-13, neutrophil and lymphocyte cell numbers, but there is no reducing the number of macrophage cells and MMP-1 expression in gingiva of Wistar rats exposed to P. gingivalis bacteria.

Immunohistochemical analysis of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 expression in the myocardium of rats in the early postnatal period on preterm birth modeling

Immunohistochemical analysis of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 expression in the myocardium of rats in the early postnatal period on preterm birth modeling

Matrix Metalloproteinase 1 Acts as an Independent Prognostic Biomarker Correlated with Immune Infiltration in Breast Cancer

Matrix metalloproteinase 1 (MMP1) is overexpressed in multiple human tumors. However, the role of MMP1 in breast cancer (BRCA) has not been explored. The relationship between MMP1 expression and immune cell infiltration was conducted using Tumor Immune Estimation Resource (TIMER, &lt;ext-link ext-link-type="uri" xlink:href="https://cistrome.shinyapps.io/timer/"&gt;https://cistrome.shinyapps.io/timer/&lt;/ext-link&gt;), and the survival curve was plotted using Kaplan-Meier with log-rank test. The influence of MMP1 on immune infiltration, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, immunologic infiltration analysis, and drug sensitivity were conducted through R 4.2.0. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to verify MMP1 expression in BC and the correlation between MMP1 and CD20, CD86 immune cells. MMP1 was overexpressed in BRCA tumors (P &lt; 0.05), and its high expression was related to poor prognosis (P = 0.01). In addition, MMP1 was an independent prognostic biomarker in BRCA. Our findings provide information to further understand the biological functions and signaling pathways of MMP1 in BRCA. IHC and IF have proven the relationship between MMP1 and BRCA. These results implied a critical role of MMP1 in the prognosis and immune infiltration of BRCA. In addition, MMP1 expression participated in regulating multiple oncogenes and tumorigenesis.

Exogenous autoinducer-2 alleviates intestinal damage in necrotizing enterocolitis via PAR2/MMP3 signaling pathway

BackgroundImbalanced intestinal microbiota and damage to the intestinal barrier contribute to the development of necrotizing enterocolitis (NEC). Autoinducer-2 (AI-2) plays a crucial role in repairing intestinal damage and reducing inflammation. ObjectiveThis study aimed to investigate the impact of AI-2 on the expression of intestinal zonula occludens-1 (ZO-1) and occludin proteins in NEC. We evaluated its effects in vivo using NEC mice and in vitro using lipopolysaccharide (LPS)-stimulated intestinal cells. MethodsPathological changes in the intestines of neonatal mice were assessed using histological staining and scoring. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to determine the optimal conditions for LPS and AI-2 interventions. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA levels of matrix metalloproteinase-3 (MMP3), protease activated receptor-2 (PAR2), interleukin-1β (IL-1β), and IL-6. Protein levels of MMP3, PAR2, ZO-1, and occludin were evaluated using western blot, immunohistochemistry, or immunofluorescence. ResultsAI-2 alleviated NEC-induced intestinal damage (P < 0.05) and enhanced the proliferation of damaged IEC-6 cells (P < 0.05). AI-2 intervention reduced the mRNA and protein expressions of MMP3 and PAR2 in intestinal tissue and cells (P < 0.05). Additionally, it increased the protein levels of ZO-1 and occludin (P < 0.05), while reducing IL-1β and IL-6 mRNA expression (P < 0.05). ConclusionAI-2 intervention enhances the expression of tight junction proteins (ZO-1 and occludin), mitigates intestinal damage in NEC neonatal mice and IEC-6 cells, potentially by modulating PAR2 and MMP3 signaling. AI-2 holds promise as a protective intervention for NEC. AI-2 plays a crucial role in repairing intestinal damage and reducing inflammation.

Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro.

The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial-mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein.

MMP13-responsive hydrogel microspheres for osteoarthritis treatment by precise delivery of celecoxib

Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.

Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway.

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1β (IL-1β), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1β, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO-1 pathway to inhibit NF-κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.