The p38 signaling pathway mediates the TGF‐β1‐induced increase in type I collagen deposition in human granulosa cells

2020 ◽  
Vol 34 (11) ◽  
pp. 15591-15604
Author(s):  
Hui Li ◽  
Hsun‐Ming Chang ◽  
Zhendan Shi ◽  
Peter C. K. Leung
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Human Granulosa Cells ◽  
Tgf Β1

scholarly journals Huiyang Shengji Extract Improve Chronic Nonhealing Cutaneous through the TGF-β1/Smad3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yan Lin ◽  
Xiujuan He ◽  
Xinran Xie ◽  
Qingwu Liu ◽  
Jia Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Chronic Wounds ◽  
Human Fibroblasts ◽  
Type Iii Collagen ◽  
Type I ◽  
Paracrine Factors ◽  
M1 Macrophages ◽  
Tgf Β1

Chronic nonhealing cutaneous wounds are a thorny problem in the field of surgery because of their prolonged and unhealed characteristics. Huiyang Shengji extract (HSE) is an extract of traditional Chinese medicine prescription for treating chronic wounds. This study aims to investigate the regulation of M1 macrophages on fibroblast proliferation and secretion and the intervention mechanism of Huiyang Shengji extract. We found that the effects of HSFs stimulated with paracrine factors from M1 macrophages were as follows: the proliferation of HSFs was reduced, the expression of MKI-67 was downregulated, and the content and gene expression of the inflammation factors and fibroblast MMPs were increased, while the content and gene expression of TIMP-1 are decreased, the content of human fibroblasts secreting type I collagen (COL1A1) and type III collagen (COL3A1) was decreased, and the TGF-β1/Smad3 signaling pathway was inhibited. Interestingly, HSE inhibited these effects of M1 macrophages on human fibroblasts after the intervention, and the inhibitory effect was related to the concentration. In conclusion, M1 macrophages caused changes in HSFs and secretion, while HSE has a specific regulatory effect on the proliferation and secretion of fibroblasts caused by M1 macrophages.

scholarly journals Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Min Liu ◽  
Youwei Xu ◽  
Xu Han ◽  
Lianhong Yin ◽  
Lina Xu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Pyrrolidine Dithiocarbamate ◽  
Type I ◽  
Tgf Β1

Abstract The present work aimed to investigate the activities and underlying mechanisms of dioscin against alcoholic liver fibrosis (ALF). In vivo liver fibrosis in mice was induced by an alcoholic liquid diet and in vitro studies were performed on activated HSC-T6 and LX2 cells treated with lipopolysaccharide. Our results showed that dioscin significantly attenuated hepatic stellate cells (HSCs) activation, improved collagen accumulation and attenuated inflammation through down-regulating the levels of myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), interleukin (IL)-1, IL-6 and tumour necrosis factor-α by decreasing Toll-like receptor (TLR)4 expression both in vivo and in vitro. TLR4 overexpression was also decreased by dioscin, leading to the markedly down-regulated levels of MyD88, NF-κB, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) in cultured HSCs. Suppression of cellular MyD88 by ST2825 or abrogation of NF-κB by pyrrolidine dithiocarbamate eliminated the inhibitory effects of dioscin on the levels of TGF-β1, α-SMA and COL1A1. In a word, dioscin exhibited potent effects against ALF via altering TLR4/MyD88/NF-κB signaling pathway, which provided novel insights into the mechanisms of this compound as an antifibrogenic candidate for the treatment of ALF in the future.

Hepatic fibrosis and gene expression changes induced by praziquantel treatment during immune modulation of Schistosoma japonicum infection

Parasitology ◽  
1993 ◽  
Vol 107 (4) ◽  
pp. 397-404 ◽  
Author(s):  
T. F. Kresina ◽  
Qing He ◽  
S. Degli Esposti ◽  
M. A. Zern
Keyword(s):  
Gene Expression ◽  
Schistosoma Japonicum ◽  
Immune Modulation ◽  
Type I Collagen ◽  
Acute Infection ◽  
Collagen Content ◽  
Type I ◽  
Collagen Deposition ◽  
Hepatic Fibrogenesis ◽  
Tgf Β1

SUMMARYIn the present study fibrogenic gene expression was determined in murine Schistosoma japonicum infection during the progression of immune modulation of infection and following chemotherapy during the course of immune modulation. Histomorphometric analysis of granuloma size and collagen deposition revealed peak granuloma size in acute infection (5 weeks) and peak hepatic collagen content at 16 weeks of infection. Peak Type I collagen gene expression was concomitant with TGF-β1 gene expression at 8–11 weeks. Chemotherapy during either acute (9 weeks) or chronic (24, 28 weeks) infection resulted in increased collagen deposition and increased gene expression of Type I collagen and TGF-β1. However, chemotherapy at 14–16 weeks resulted in decreased levels of TGF-β1 gene expression and essentially minimal change in Type I collagen deposition and gene expression. These data indicate that chemotherapy of schistosomiasis japonica does not reverse hepatic fibrogenesis when administered in acute infection – when granuloma size is maximal – or in chronic infection. However, a beneficial effect on hepatic fibrogenesis is seen when chemotherapy is administered at 14–16 weeks post-infection, a time of decreasing granuloma size and maximal hepatic collagen content. Thus the ability to reverse schistosomal-induced hepatic fibrogenesis by chemotherapy may depend on disease stage.

scholarly journals A Human Cellular Model for Colorectal Anastomotic Repair: The Effect of Localization and Transforming Growth Factor-β1 Treatment on Collagen Deposition and Biomarkers

2021 ◽  
Vol 22 (4) ◽  
pp. 1616
Author(s):  
Ceylan Türlü ◽  
Nicholas Willumsen ◽  
Debora Marando ◽  
Peter Schjerling ◽  
Edyta Biskup ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Mrna Levels ◽  
Cellular Model ◽  
Collagen Deposition ◽  
Total Collagen ◽  
Tgf Β1

Anastomotic leakage (AL) is a devastating complication after colorectal surgery, possibly due to the loss of stabilizing collagen fibers in the submucosa. Our aim was to assess the formation of collagen in the colon versus the rectum with or without transforming growth factor (TGF)-β1 exposure in a human cellular model of colorectal repair. Primary fibroblasts were isolated by an explant procedure from clinically resected tissue rings during anastomosis construction in 19 consecutive colorectal patients who underwent laparoscopy. The cells, identified as fibroblasts by morphologic characteristics and flow cytometry analysis (CD90+), were cultured for 8 days and in 12 patients in the presence of 1 ng/mL TGF-β1. Total collagen deposition was measured colorimetrically after Sirius red staining of fixed cell layers, and type I, III, and VI collagen biosynthesis and degradation were specifically determined by the biomarkers PINP, PRO-C3, PRO-C6, and C3M in conditioned media by competitive enzyme-linked immunosorbent assays. Total collagen deposition by fibroblasts from the colon and rectum did not significantly differ. TGF-β1 treatment increased PINP, PRO-C6, and total collagen deposition. Mechanistically, TGF-β1 treatment increased COL1A1 and ACTA2 (encoding α-smooth muscle actin), and decreased COL6A1 and MMP2 mRNA levels in colorectal fibroblasts. In conclusion, we found no effect of anatomic localization on collagen production by fibroblasts derived from the large intestine. TGF-β1 represents a potential therapeutic agent for the prevention of AL by increasing type I collagen synthesis and collagen deposition.

Mutation of the 5' untranslated region stem-loop mRNA structure reduces type I collagen deposition and arterial stiffness in male obese mice

2021 ◽  
Author(s):  
Francisco I. Ramirez-Perez ◽  
Makenzie L. Woodford ◽  
Mariana Morales-Quinones ◽  
Zachary I. Grunewald ◽  
Francisco J Cabral-Amador ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Arterial Stiffness ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Wild Type ◽  
Stem Loop ◽  
Arterial Stiffening

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden. A major contributor to arterial stiffening is increased collagen deposition. In the 5' untranslated regions of mRNAs encoding for type I collagen, an evolutionally conserved stem-loop (SL) structure plays an essential role in its stability and post-transcriptional regulation. Here, we show that feeding a high fat/high sucrose (HFHS) diet for 28 weeks increases adiposity, insulin resistance, and blood pressure in male wild-type littermates. Moreover, arterial stiffness, assessed in vivo via aortic pulse wave velocity, and ex vivo using atomic force microscopy in aortic explants or pressure myography in isolated femoral and mesenteric arteries, was also increased in those mice. Notably, all these indices of arterial stiffness, along with collagen type I levels in the vasculature, were reduced in HFHS-fed mice harboring a mutation in the 5'SL structure, relative to wild-type littermates. This protective vascular phenotype in 5'SL-mutant mice did not associate with a reduction in insulin resistance or blood pressure. These findings implicate the 5'SL structure as a putative therapeutic target to prevent or reverse arterial stiffening and CVD associated with obesity and type 2 diabetes.

scholarly journals BMP15 Suppresses Progesterone Production by Down-Regulating StAR via ALK3 in Human Granulosa Cells

2013 ◽  
Vol 27 (12) ◽  
pp. 2093-2104 ◽  
Author(s):  
Hsun-Ming Chang ◽  
Jung-Chien Cheng ◽  
Christian Klausen ◽  
Peter C. K. Leung
Keyword(s):  
Granulosa Cells ◽  
Critical Role ◽  
Regulatory Protein ◽  
Granulosa Cell Tumor ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Human Granulosa Cells ◽  
Progesterone Production ◽  
Steroidogenic Acute Regulatory

In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD)1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.

scholarly journals Mesenchymal Stromal Cells Derived Conditioned Medium in Pulmonary Fibrosis: A Systematic Review and Meta-analysis

2020 ◽  
Vol 23 (12) ◽  
pp. 870-879
Author(s):  
Kosar Mohamed Ali ◽  
Fattah Hama Rahim Fattah ◽  
Shirwan Hamasalh Omar ◽  
Mohammed I M Gubari ◽  
Mahmoud Yousefifard ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interleukin 6 ◽  
Meta Analysis ◽  
Type Iii Collagen ◽  
Type I ◽  
Collagen Deposition ◽  
Tgf Β1

Background: A definitive conclusion on the efficacy of mesenchymal stromal cells-derived conditioned medium (MSCs-CM) in pulmonary fibrosis has not yet been reached. Therefore, the present meta-analysis intends to investigate the efficacy of MSCs-CM administration on improvement of pulmonary fibrosis. Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of August 2019. Outcomes in the present study included pulmonary fibrosis score, lung collagen deposition, lung collagen expression, transforming growth factor β1 (TGF-β1) expression and interleukin-6 expression. Finally, the data were pooled and an overall standardized mean difference (SMD) with a 95% confidence interval (CI) was reported. Results: Data from seven studies were included. Analyses showed that administration of MSCs-CM significantly improved pulmonary fibrosis (SMD = -2.36; 95% CI: -3.21, -1.51). MSCs-CM administration also attenuated lung collagen deposition (SMD = -1.70; 95% CI: -2.18, -1.23) and decreased expression of type I collagen (SMD = -6.27; 95% CI: -11.00, -1.55), type III collagen (SMD = -5.16; 95% CI: -9.86, -0.47), TGF- β1 (SMD = -3.36; 95% CI: - 5.62, -1.09) and interleukin-6 (SMD = -1.69; 95% CI: - 3.14, -0.24). Conclusion: The present meta-analysis showed that administration of MSCs-CM improves pulmonary fibrosis. It seems that the effect of MSCs-CM was mediated by reducing collagen deposition as well as inhibiting the production of inflammatory chemokines such as TGF-β1 and interleukin 6 (IL-6). Since there is no evidence on the efficacy of MSCs-CM in large animals, further studies are needed to translate the finding to clinical studies.

scholarly journals Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianxia Wen ◽  
Dan Wang ◽  
Jian Wang ◽  
Ruilin Wang ◽  
Shizhang Wei ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Oral Treatment ◽  
High Mobility ◽  
High Mobility Group ◽  
Type I ◽  
Mrna Levels ◽  
Inflammatory Signaling ◽  
Astragali Radix

Astragali Radix (AR), the dried root of Astragali Radix membranaceus (Fisch.) Bge. or Astragali Radix membranaceus (Fisch.) Bge. var. mongholicus (Bge) Hsiao, is a commonly used traditional Chinese medicine for the treatment of liver diseases. This study aimed to comprehensively evaluate the pharmacological action and explore the potential mechanism of AR on liver fibrosis. Rats were administered with carbon tetrachloride for eight weeks, followed by oral treatment with AR for six weeks. The efficacy was confirmed by measuring liver function and liver fibrosis levels. The underlying mechanisms were explored by detecting the expression of related proteins. AR significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (COL-IV), hyaluronic acid (HA), laminin (LN), and precollagen type III (PCIII). In addition, AR inhibited the deposition of collagen and the activation of hepatic stellate cells. Those data strongly demonstrated that AR alleviated liver fibrosis by CCl4. In order to illustrate the potential inflammatory, the mRNA levels of IL-6, TNF-α, and IL-1β were detected. Subsequently, immunohistochemistry analysis was performed to further verify the expression of type I collagen. Finally, the expression of key proteins in the inflammatory signaling pathway was detected. AR significantly reduced the expression of high-mobility group box 1 (HMGB1), TLR4, Myd88, RAGE, and NF-κ B p65 genes and proteins. In addition, western blotting showed AR decreased the protein expression of RAGE, p-MEK1/2, p-ERK1/2, and p-c-Jun. Taken together, our data reveal that AR significantly inhibits liver fibrosis by intervening in the HMGB1-mediated inflammatory signaling pathway and secretion signaling pathway. This study will provide valuable references for the in-depth research and development of Astragali Radix against liver fibrosis.

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