scholarly journals Insulin-like Growth Factor-I Signaling Mechanisms, Type I Collagen and Alpha Smooth Muscle Actin in Human Fetal Lung Fibroblasts

2006 ◽  
Vol 60 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Anne Chetty ◽  
Gong-Jee Cao ◽  
Heber C Nielsen
Keyword(s):  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Type I ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Factor I ◽  
Signaling Mechanisms ◽  
Human Fetal Lung

scholarly journals The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1861
Author(s):  
Jemima Seidenberg ◽  
Mara Stellato ◽  
Amela Hukara ◽  
Burkhard Ludewig ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Beclin 1 ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Background: Pathological activation of cardiac fibroblasts is a key step in development and progression of cardiac fibrosis and heart failure. This process has been associated with enhanced autophagocytosis, but molecular mechanisms remain largely unknown. Methods and Results: Immunohistochemical analysis of endomyocardial biopsies showed increased activation of autophagy in fibrotic hearts of patients with inflammatory cardiomyopathy. In vitro experiments using mouse and human cardiac fibroblasts confirmed that blockade of autophagy with Bafilomycin A1 inhibited fibroblast-to-myofibroblast transition induced by transforming growth factor (TGF)-β. Next, we observed that cardiac fibroblasts obtained from mice overexpressing transcription factor Fos-related antigen 2 (Fosl-2tg) expressed elevated protein levels of autophagy markers: the lipid modified form of microtubule-associated protein 1A/1B-light chain 3B (LC3BII), Beclin-1 and autophagy related 5 (Atg5). In complementary experiments, silencing of Fosl-2 with antisense GapmeR oligonucleotides suppressed production of type I collagen, myofibroblast marker alpha smooth muscle actin and autophagy marker Beclin-1 in cardiac fibroblasts. On the other hand, silencing of either LC3B or Beclin-1 reduced Fosl-2 levels in TGF-β-activated, but not in unstimulated cells. Using a cardiac hypertrophy model induced by continuous infusion of angiotensin II with osmotic minipumps, we confirmed that mice lacking either Fosl-2 (Ccl19CreFosl2flox/flox) or Atg5 (Ccl19CreAtg5flox/flox) in stromal cells were protected from cardiac fibrosis. Conclusion: Our findings demonstrate that Fosl-2 regulates autophagocytosis and the TGF-β-Fosl-2-autophagy axis controls differentiation of cardiac fibroblasts. These data provide a new insight for the development of pharmaceutical targets in cardiac fibrosis.

scholarly journals Age-Dependent Expression of Collagen Receptors and Deformation of Type I Collagen Substrates by Rat Cardiac Fibroblasts

2011 ◽  
Vol 17 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Christopher G. Wilson ◽  
John W. Stone ◽  
Vennece Fowlkes ◽  
Mary O. Morales ◽  
Catherine J. Murphy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Β1 Integrin ◽  
Alpha Smooth Muscle Actin ◽  
Collagen Receptors ◽  
Age Dependent ◽  
Adult Cells

AbstractLittle is known about how age influences the ways in which cardiac fibroblasts interact with the extracellular matrix. We investigated the deformation of collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer and three-dimensional (3D) cultures, and quantified the expression of three collagen receptors [discoidin domain receptor (DDR)1, DDR2, and β1 integrin] and the contractile protein alpha smooth muscle actin (α-SMA) in these cells. We report that adult fibroblasts contracted 3D collagen substrates significantly less than their neonate counterparts, whereas no differences were observed in monolayer cultures. Adult cells had lower expression of β1 integrin and α-SMA than neonate cultures, and we detected significant correlations between the expression of α-SMA and each of the collagen receptors in neonate cells but not in adult cells. Consistent with recent work demonstrating age-dependent interactions with myocytes, our results indicate that interactions between cardiac fibroblasts and the extracellular matrix change with age.

A preliminary study of uterine scar tissue following cesarean section

2018 ◽  
Vol 46 (4) ◽  
pp. 379-386 ◽  
Author(s):  
Cailin Wu ◽  
Xin Chen ◽  
Zhixiong Mei ◽  
Juan Zhou ◽  
Liangzhi Wu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cesarean Section ◽  
Cesarean Delivery ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Scar Tissue ◽  
Volume Density ◽  
Lower Uterine Segment ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Abstract Aim: To compare smooth muscle cells, type I collagen, and apoptosis of the lower uterine segment of women who had/without a prior cesarean delivery. Methods: Alpha smooth muscle actin (α-SMA), type I collagen, and nuclear apoptosis were compared between the groups from lower uterine segment. Twenty-eight controls and 82 with one prior cesarean delivery were included. The women with a prior cesarean section were classified by time since the surgery: ≤3 years, >3 and ≤5 years, >5 and ≤7 years, >7 and ≤9 years, and >9 years. Results: Smooth muscle volume density (VD) % was significantly lower in women who had cesarean sections in first three groups than in the controls (all, P<0.01). Type I collagen VD% was similar among all groups and the controls. The number of apoptotic nuclei in the lower uterine segment of the scarred group was greater up to 3 years after surgery and less than in the control at 7–9 years. The number of non-apoptotic nuclei in the scarred group was greater than controls up to 7 years after surgery. Conclusion: The lower uterine segment scar becomes stable at 3 years after cesarean delivery, and by 9 years, the scar is mature.

Bradykinin augments fibroblast-mediated contraction of released collagen gels

2001 ◽  
Vol 281 (1) ◽  
pp. L164-L171 ◽  
Author(s):  
Tadashi Mio ◽  
Xiangde Liu ◽  
Myron L. Toews ◽  
Yuichi Adachi ◽  
Debra J. Romberger ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Type I Collagen ◽  
Inflammatory Diseases ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Type I ◽  
Dependent Manner ◽  
Collagen Gels ◽  
Protein Kinase C Inhibitors

Bradykinin is a multifunctional mediator of inflammation believed to have a role in asthma, a disorder associated with remodeling of extracellular connective tissue. Using contraction of collagen gels as an in vitro model of wound contraction, we assessed the effects of bradykinin tissue on remodeling. Human fetal lung fibroblasts were embedded in type I collagen gels and cultured for 5 days. After release, the floating gels were cultured in the presence of bradykinin. Bradykinin significantly stimulated contraction in a concentration- and time-dependent manner. Coincubation with phosphoramidon augmented the effect of 10−9 and 10−8 M bradykinin. A B2 receptor antagonist attenuated the effect of bradykinin, whereas a B1 receptor antagonist had no effect, suggesting that the effect is mediated by the B2 receptor. An inhibitor of intracellular Ca2+mobilization abolished the response; addition of EGTA to the culture medium attenuated the contraction of control gels but did not modulate the response to bradykinin. In contrast, the phospholipase C inhibitor U-73122 and the protein kinase C inhibitors staurosporine and GF-109203X attenuated the responses. These data suggest that by augmenting the contractility of fibroblasts, bradykinin may have an important role in remodeling of extracellular matrix that may result in tissue dysfunction in chronic inflammatory diseases, such as asthma.

Selective Migration of α-Smooth Muscle Actin-Positive Myofibroblasts toward Fibronectin in the Boyden's Blindwell Chamber

1997 ◽  
Vol 93 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Masashi Kawamoto ◽  
Takakuni Matsunami ◽  
Ronald F. Ertl ◽  
YUH Fukuda ◽  
Maki Ogawa ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Immunoelectron Microscopy ◽  
Smooth Muscle Actin ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Migration Assay ◽  
Total Proportion ◽  
Bottom Side ◽  
Actin Expression ◽  
Human Fetal Lung

1. In order to address the hypothesis that migrating fibroblasts have a different phenotype, human fetal lung fibroblasts (HFL-1) cells were evaluated in the Boyden blindwell chamber migration assay followed by immunoelectron microscopy. 2. HFL-1 cells were placed on nucleopore filters and incubated for 2 h using purified human plasma fibronectin (pFn) as a chemoattractant. Filters were then processed for immunoelectron microscopy using antibodies for α-smooth muscle (α-SM) actin as a marker for myofibroblasts, cellular fibronectin (cFn) and VLA-5. 3. Cells which had migrated to the bottom side of the filter were more likely to express α-SM actin, 29.1 ± 3.4% of cells, compared with cells which did not migrate through the filter, 12.4 ± 1.3% (P < 0.05). The total proportion of α-SM-actin-positive cells located on both sides of the filter showed no difference between those which had migrated toward pFn and controls (17.7 ± 1.0% compared with 20.2 ± 2.5%). 4. cFn-positive cells showed minimal differences compared with control cells, while perinuclear and endoplasmic reticulum staining of VLA-5 was observed only in the cells treated with pFn. 5. The results show that HFL-1 cells are heterogenous for α-SM actin expression. Short-term incubation with pFn did not change the proportion of α-SM-actin-positive HFL-1 cells. Cells which migrate, however, are enriched for α-SM actin expression. pFn-induced fibroblast chemotaxis can selectively recruit myofibroblasts with increased α-SM actin expression, a feature which may contribute to the altered population of cells at sites of fibrosis.

IGF-I and TGF-β1 have distinct effects on phenotype and proliferation of intestinal fibroblasts

2002 ◽  
Vol 283 (3) ◽  
pp. G809-G818 ◽  
Author(s):  
James G. Simmons ◽  
Jolanta B. Pucilowska ◽  
Temitope O. Keku ◽  
P. Kay Lund
Keyword(s):  
Smooth Muscle ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Fiber Formation ◽  
Type I ◽  
Muscle Actin ◽  
Stress Fiber Formation ◽  
Igf I ◽  
Tgf Β1

Insulin-like growth factor I (IGF-I) and transforming growth factor-β1 (TGF-β1) are upregulated in myofibroblasts at sites of fibrosis in experimental enterocolitis and in Crohn's disease (CD). We compared the sites of expression of IGF-I and TGF-β1 in a rat peptidoglycan-polysaccharide (PG-PS) model of chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD-18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-β1 and IGF-I interact to regulate proliferation, collagen synthesis, and activated phenotype typified by expression of α-smooth muscle actin and organization into stress fibers. IGF-I potently stimulated while TGF-β1 inhibited basal DNA synthesis. TGF-β1 and IGF-I each had similar but not additive effects to induce type I collagen. TGF-β1 but not IGF-I potently stimulated expression of α-smooth muscle actin and stress fiber formation. IGF-I in combination with TGF-β1 attenuated stress fiber formation without reducing α-smooth muscle actin expression. Stress fibers were not a prerequisite for increased collagen synthesis. TGF-β1 upregulated IGF-I mRNA, which led us to examine the effects of IGF-I in cells previously activated by TGF-β1 pretreatment. IGF-I potently stimulated proliferation of TGF-β1-activated myofibroblasts without reversing activated fibrogenic phenotype. We conclude that TGF-β1 and IGF-I both stimulate type I collagen synthesis but have differential effects on activated phenotype and proliferation. We propose that during intestinal inflammation, regulation of activated phenotype and proliferation may require sequential actions of TGF-β1 and IGF-I, but they may act in concert to increase collagen deposition.

scholarly journals LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p

2017 ◽  
Vol 41 (5) ◽  
pp. 1970-1980 ◽  
Author(s):  
Fujun Yu ◽  
Yong Guo ◽  
Bicheng Chen ◽  
Liang Shi ◽  
Peihong Dong ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Noncoding Rna ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Type I ◽  
Muscle Actin ◽  
Pathway Activity ◽  
Long Intergenic Noncoding Rna

Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.

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