scholarly journals Gene suppression of the ClC-2 chloride channel suppressed TGF-β1-induced proliferation, collagen synthesis, and collagen gel contraction mediated by conjunctival fibroblasts

2020 ◽  
Author(s):  
lixia sun ◽  
Renzhe Cui ◽  
huan meng ◽  
Xiwen Liu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Chloride Channel ◽  
Collagen Synthesis ◽  
Collagen Gel ◽  
Gene Suppression ◽  
Collagen Gel Contraction ◽  
Tgf Β1

scholarly journals Role of the ClC-2 Chloride Channel in TGF-β1-induced Proliferation, Collagen Synthesis, and Collagen Gel Contraction Mediated by Human Conjunctival Fibroblasts

2020 ◽  
Author(s):  
Lixia Sun ◽  
Renzhe chui ◽  
Meng Huan ◽  
Xiwen Liu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Cell Cycle Progression ◽  
Collagen Synthesis ◽  
Collagen Gel ◽  
Sirna Transfection ◽  
Collagen Gel Contraction ◽  
Tgf Β1

Abstract Background: Excessive scar tissue can reduce postoperative survival of filtering blebs in patients with glaucoma. Previous studies have highlighted the role of chloride channels in wound healing. whereas The role of chloride channels in the formation of follicular scar has not been studied. Objectives: To investigate the effects of the ClC-2 chloride channel on scar formation of filtering blebs after glaucoma filtering surgery. Methods: We Inhibited ClC-2 chloride channels of Human Conjunctival Fibroblasts (HConFs) by transfecting HConFs with ClC-2 siRNA, Then cell proliferation, cycle and collagen synthesis of HConFs were measured. ClC-2 siRNA-transfected HConFs were cultured in type I collagen gels in the presence of transforming growth factor (TGF)-β1. Collagen gel contraction was evaluated based on the gel area. The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in HConFs were assessed by western blotting and q-PCR. Results: TGF-β1induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction in HConFs. TGF-β1 increased MMP-2 and MMP-9 levels but inhibited the expression of TIMPs. ClC-2 siRNA transfection inhibited TGF-β1-induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction, mediated by HConFs. TGF-β1-induced increases in MMP-2 and MMP-9 were also inhibited by NPPB and ClC-2 siRNA transfection, but TIMP expression was increased by ClC-2 siRNA transfection. Conclusions: These findings demonstrate that ClC-2 gene knockout inhibited TGF-β1-induced cell proliferation, collagen synthesis, and collagen gel contraction of HConFs by attenuating MMP-2 and MMP-9 production and by stimulating TIMP-1 production. Keywords: ClC-2 chloride channel; conjunctival fibroblasts; TGF-β1; wound heal

In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-β1-induced collagen gel contraction

Cytokine ◽  
2020 ◽  
pp. 155359
Author(s):  
S. Bolivar ◽  
J.A. Espitia-Corredor ◽  
F. Olivares-Silva ◽  
P. Valenzuela ◽  
C. Humeres ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Interferon Beta ◽  
Cardiac Fibroblasts ◽  
Collagen Gel ◽  
Collagen Gel Contraction ◽  
Tgf Β1

Gallic acid attenuates TGF-β1-stimulated collagen gel contraction via suppression of RhoA/Rho-kinase pathway in hypertrophic scar fibroblasts

Life Sciences ◽  
2016 ◽  
Vol 161 ◽  
pp. 19-26 ◽  
Author(s):  
Shu-Chung Hsieh ◽  
Chun-Chi Wu ◽  
Shih-Lan Hsu ◽  
Chin-Hsing Feng ◽  
Jung-Hsing Yen
Keyword(s):  
Gallic Acid ◽  
Hypertrophic Scar ◽  
Rho Kinase ◽  
Collagen Gel ◽  
Collagen Gel Contraction ◽  
Kinase Pathway ◽  
Tgf Β1

Smad3 mediates TGF-β1-induced collagen gel contraction by human lung fibroblasts

2006 ◽  
Vol 339 (1) ◽  
pp. 290-295 ◽  
Author(s):  
Tetsu Kobayashi ◽  
Xiangde Liu ◽  
Fu-Qiang Wen ◽  
Tadashi Kohyama ◽  
Lei Shen ◽  
...  
Keyword(s):  
Human Lung ◽  
Collagen Gel ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Collagen Gel Contraction ◽  
Tgf Β1

Abstract 348: Phorbol 12-myristate 13-acetate Induces Dedifferentiation of Cardiac Myofibroblasts to Fibroblasts and Other Unidentified Type of Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Vy Tran Luu ◽  
Sang Phan ◽  
Zhuqiu Jin
Keyword(s):  
Cardiac Fibrosis ◽  
De Novo ◽  
Cardiac Fibroblasts ◽  
Collagen Gel ◽  
Collagen Gel Contraction ◽  
Human Cardiac Fibroblasts ◽  
Multiple Cells ◽  
Tgf Β1 ◽  
Cardiac Myofibroblasts ◽  
Shape And Size

Cardiac fibrosis plays an essential role in cardiac pathogenic processes that occur as a result of myocardial infarction or hypertrophic cardiomyopathy. The differentiation of cardiac fibroblasts to myofibroblasts is considered to be a critical step in the activation and progression of cardiac fibrosis. TGFβ is one of the essential molecules that promote transition of fibroblasts to myofibroblasts. Reversal of formed myofibroblasts to fibroblasts remains incompletely understood. Phorbol 12-Myristate 13-Acetate (PMA) regulates metabolism and functions of multiple cells via PKC activation mostly. To study effects of PMA on differentiation of de novo formed cardiac myofibroblasts, human cardiac fibroblasts were utilized. Human cardiac fibroblasts (HCF) cultured in fibroblast medium (FM)-2 were converted into myofibroblasts in the presence of 2 ng/mL of TGF-β1 for 48 hours. Expression of α-SMA, the biomarker of myofibroblasts, and FSP1, the biomarker of fibroblasts, was detected using Western blot and immunofluorescence. Collagen gel contraction induced by fibroblasts was determined as well. TGF-β1 increased the expression of α-SMA and reduced the expression of FSP1. Distinct cellular morphology changes in the shape and size of HCF were observed after incubation with TGF-β1 for 48 hours. To investigate effect of PMA on dedifferentiation of formed myofibroblasts, these TGF-β1-pretreated cells were divided into four groups for additional 48 hours incubation: PMA groups (10, 50, and 100 ng/mL) or DMSO (vehicle control). Both 50 and 100 ng/mL of PMA reduced the expression of α-SMA but only 100 ng/mL of PMA increased the expression of FSP1. The shape and size of cells changed after treatment with PMA. PMA also reduced TGF-β1-induced collagen gel contraction (P<0.05, compared to DMSO group). These data indicated that PMA can reverse the differentiation of de novo formed human cardiac myofibroblasts induced by TGF-β1 to fibroblasts and other unidentified type of cells. Although the mechanism of dedifferentiation remains to be identified, the novel finding of this study shed light on future development of agents to treat fibrotic diseases.

scholarly journals Tropomyosin 2.1 collaborates with fibronectin to promote TGF-β1-induced contraction of human lung fibroblasts

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peta Bradbury ◽  
Cassandra P. Nader ◽  
Aylin Cidem ◽  
Sandra Rutting ◽  
Dianne Sylvester ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Human Lung ◽  
Collagen Gel ◽  
Protein Profiling ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Collagen Gel Contraction ◽  
The Matrix ◽  
Cytokine Stimulation ◽  
Tgf Β1

AbstractMany lung diseases are characterized by fibrosis, leading to impaired tissue patency and reduced lung function. Development of fibrotic tissue depends on two-way interaction between the cells and the extra-cellular matrix (ECM). Concentration-dependent increased stiffening of the ECM is sensed by the cells, which in turn increases intracellular contraction and pulling on the matrix causing matrix reorganization and further stiffening. It is generally accepted that the inflammatory cytokine growth factor β1 (TGF-β1) is a major driver of lung fibrosis through the stimulation of ECM production. However, TGF-β1 also regulates the expression of members of the tropomyosin (Tm) family of actin associating proteins that mediate ECM reorganization through intracellular-generated forces. Thus, TGF-β1 may mediate the bi-directional signaling between cells and the ECM that promotes tissue fibrosis. Using combinations of cytokine stimulation, mRNA, protein profiling and cellular contractility assays with human lung fibroblasts, we show that concomitant induction of key Tm isoforms and ECM by TGF-β1, significantly accelerates fibrotic phenotypes. Knocking down Tpm2.1 reduces fibroblast-mediated collagen gel contraction. Collectively, the data suggest combined ECM secretion and actin cytoskeleton contractility primes the tissue for enhanced fibrosis. Our study suggests that Tms are at the nexus of inflammation and tissue stiffening. Small molecules targeting specific Tm isoforms have recently been designed; thus targeting Tpm2.1 may represent a novel therapeutic target in lung fibrosis.

scholarly journals Pirfenidone attenuates lung fibrotic fibroblast-mediated fibrotic responses to transforming growth factor-β1

2018 ◽  
Author(s):  
Jin Jin ◽  
Shinsaku Togo ◽  
Kotaro Kadoya ◽  
Miniwan Tulafu ◽  
Yukiko Namba ◽  
...  
Keyword(s):  
Growth Factor ◽  
Therapeutic Target ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Collagen Gel ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Collagen Gel Contraction ◽  
Tgf Β1

AbstractPirfenidone, an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis (IPF), functions by inhibiting myofibroblast differentiation, which is involved in transforming growth factor (TGF)-β1-induced IPF pathogenesis. However, unlike normal lung fibroblasts, the relationship between pirfenidone responses of TGF-β1-induced human fibrotic lung fibroblasts and lung fibrosis is unknown. Here, we investigated the effect of pirfenidone on the functions of two new targets, collagen triple helix repeat containing protein 1 (CTHRC1) and four-and-a-half LIM domain protein 2 (FHL2), which included fibroblast activity, collagen gel contraction, and migration toward fibronectin. Compared to control lung fibroblasts, pirfenidone restored TGF-β1-stimulated fibroblast-mediated collagen gel contraction, migration, and CTHRC1 release in lung fibrotic fibroblasts. Furthermore, pirfenidone attenuated TGF-β1- and CTHRC1-induced fibroblast activity, bone morphogenic protein-4/Gremlin1 upregulation, and α-smooth muscle actin, fibronectin, and FHL2 downregulation, similar to that observed post-CTHRC1 inhibition. In contrast, FHL2 inhibition suppressed migration and fibronectin expression but did not downregulate CTHRC1. Overall, pirfenidone suppressed fibrotic fibroblast-mediated fibrotic processes via inverse regulation of CTHRC1-induced lung fibroblast activity. Thus, CTHRC1 can be used for predicting pirfenidone response and developing new therapeutic target for lung fibrosis.Summary statementPirfenidone suppressed TGF-β1-mediated fibrotic processes in fibrotic lung fibroblasts by attenuating CTHRC1 expression, suggesting that CTHRC1 may be a novel therapeutic target for treating patients with lung fibrosis.

Urotensin-2 promotes collagen synthesis via ERK1/2-dependent and ERK1/2-independent TGF-β1 in neonatal cardiac fibroblasts

2011 ◽  
Vol 35 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Hong‑Yan Dai ◽  
Tao He ◽  
Xiao‑Lu Li ◽  
Wen‑Liang Xu ◽  
Zhi‑Ming Ge
Keyword(s):  
Collagen Synthesis ◽  
Cardiac Fibroblasts ◽  
Tgf Β1
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