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.

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 Arg-Gly-Asp-containing peptides expose novel collagen receptors on fibroblasts: implications for wound healing.

1991 ◽  
Vol 2 (12) ◽  
pp. 1035-1044 ◽  
Author(s):  
M V Agrez ◽  
R C Bates ◽  
A W Boyd ◽  
G F Burns
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Type I Collagen ◽  
Regulatory Control ◽  
Type I ◽  
Collagen Gels ◽  
Collagen Matrices ◽  
Surface Receptors ◽  
Rgd Sequence ◽  
Collagen Receptors

Integrins are a family of cell-surface receptors intimately involved in the interactions of cells with their extracellular matrix. These receptors comprise an alpha and beta subunit in noncovalent association and many have been shown to recognize and bind an arginine-glycine-aspartate (RGD) sequence contained within their specific extracellular matrix ligand. Fibroblasts express integrin receptors belonging to two major subfamilies. Some of the members within the subfamily defined by beta 1 (VLA) are receptors for collagen but, perhaps surprisingly, the other major subfamily of integrins on fibroblasts--that defined by the alpha chain of the vitronectin receptor, alpha v--all appear to bind primarily vitronectin and/or fibronectin. In the present study we show that RGD-containing peptides expose cryptic binding sites on the alpha v-associated integrins enabling them to function as collagen receptors. The addition of RGD-containing peptides to fibroblasts cultured on type I collagen induced dramatic cell elongation and, when the cells were contained within collagen matrices, the peptides induced marked contraction of the gels. These processes were inhibited by Fab fragments of a monoclonal antibody against an alpha v integrin. Also, alpha v-associated integrins from cell lysates bound to collagen I affinity columns in the presence, but not in the absence, of RGD-containing peptides. These data suggest a novel regulatory control for integrin function. In addition, because the cryptic collagen receptors were shown to be implicated in the contraction of collagen gels, the generation of such binding forces suggests that this may be the major biological role for these integrins in processes such as wound healing.

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.

scholarly journals Pen-strep influence macrophage mechanical property and mechano-response to microenvironment

2020 ◽  
Author(s):  
Weikang Zhao ◽  
Buwei Hu ◽  
Xuexiang Zhang ◽  
Pingping Wang
Keyword(s):  
Mechanical Property ◽  
Extracellular Matrix ◽  
Type I Collagen ◽  
Type I ◽  
Β1 Integrin ◽  
Rgd Peptides ◽  
Coated Surface ◽  
Cell Elasticity ◽  
Mediate Cell ◽  
Cell Spread

AbstractPenicillin-streptomycin (Pen-strep) is a common antibiotic used to prevent bacterial infection in cell culture and clinical treatment. Current research found pen-strep increased macrophage modulus but limited influence on cell adhesion. Phalloidin statin image indicates pen-strep mediate cell morphology on different extracellular matrix coated surface. The roundness analyzes further illustrated pen-strep promote cell spread on PDMS rubber, type I collagen, laminin, poly amino acid, poly-RGD peptides. Finally, YAP-1 and TAZ upregulation and β1 integrin downregulation may be the causes of cell elasticity and mechano-response to extracellular matrix (ECM) change.

scholarly journals Endometriotic Peritoneal Fluid Promotes Myofibroblast Differentiation of Endometrial Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Zhenzhen Zhang ◽  
Luxuan Suo ◽  
Yabing Chen ◽  
Li Zhu ◽  
Guiping Wan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peritoneal Fluid ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Collagen I ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Alpha Smooth Muscle Actin

During the development of endometriosis, the presence of fibrotic tissues in and surrounding endometriotic lesions may lead to subsequent adhesion, anatomic distortion, and chronic pain. Therefore, studies aimed at clarifying the underlying mechanisms of fibrogenesis in endometriosis could potentially provide a novel strategy for effective treatment. Mesenchymal stem cells (MSCs) play a key role in fibrotic diseases by differentiating into myofibroblasts in appropriate microenvironment. In this study, we collected endometrial and endometriotic tissues from patients with endometriosis (n=32) and control patients without endometriosis (n=20) to compare the expression of fibrotic proteins and investigate the effect of endometriotic peritoneal fluid (PF) on myofibroblast differentiation of endometrial MSCs. We found that the expression of fibrotic proteins, including alpha-smooth muscle actin (α-SMA), type I collagen (collagen I), connective tissue growth factor (CTGF), and fibronectin, and the extent of fibrosis extremely enhanced in ectopic endometria compared with eutopic endometria from the same patients with endometriosis and normal endometria from patients without endometriosis. We next isolated and identified endometrial MSCs and found that treatment with endometriotic PF strongly induced endometrial MSCs to differentiate into myofibroblasts concomitant with the activation of Smad2/3. Moreover, ectopic endometrial MSCs expressed elevated collagen I, α-SMA, fibronectin, and CTGF. Sushi domain containing-2 (SUSD2), a marker of endometrial MSCs, and α-SMA, a well-recognized marker for myofibroblasts, colocalized extensively in ectopic endometria while seldom in normal and eutopic endometria. These findings suggest that ectopic endometrial MSCs are probably more susceptible to myofibroblast differentiation because of the long-term influence of endometriotic PF. All together, we report for the first time that endometriotic PF promotes myofibroblast differentiation of endometrial MSCs. This understanding will greatly improve our understanding of the pathophysiology of endometriosis and help design better therapeutics.

scholarly journals Development of a Human Intestinal Organoid Model for In Vitro Studies on Gut Inflammation and Fibrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Leonidas Kandilogiannakis ◽  
Eirini Filidou ◽  
Ioannis Drygiannakis ◽  
Gesthimani Tarapatzi ◽  
Stylianos Didaskalou ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Collagen Type ◽  
Intestinal Inflammation ◽  
Smooth Muscle Actin ◽  
Embryonic Stem Cell Line ◽  
Embryonic Stem ◽  
Type I ◽  
Alpha Smooth Muscle Actin ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in vitro models for the preclinical evaluation of anti-inflammatory and antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 3D in vitro model derived from pluripotent stem cells, have the advantage to closely resemble the architecture of the intestinal mucosa. However, the appropriate timing for the study of inflammatory and fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs from the human embryonic stem cell line, H1, and examined the expression of mesenchymal markers during their maturation process. We also investigated the effect of inflammatory stimuli on the expression of fibrotic and immunological mediators. Serial evaluation of the expression of mesenchymal and extracellular matrix (ECM) markers revealed that HIOs have an adequately developed mesenchymal component, which gradually declines through culture passages. Specifically, CD90, collagen type I, collagen type III, and fibronectin were highly expressed in early passages but gradually diminished in late passages. The proinflammatory cytokines IL-1α and TNF-α induced the mRNA expression of fibronectin, collagen types I and III, tissue factor (TF), and alpha-smooth muscle actin (α-SMA) primarily in early passages. Similarly, HIOs elicited strong mRNA and protein mesenchymal (CXCL10) and epithelial (CXCL1, CCL2, CXCL8, and CCL20) chemokine responses in early but not late passages. In contrast, the epithelial tight junction components, CLDN1 and JAMA, responded to inflammatory stimulation independently of the culture passage. Our findings indicate that this HIO model contains a functional mesenchymal component, during early passages, and underline the significance of the mesenchymal cells’ fitness in inflammatory and fibrotic responses. Therefore, we propose that this model is suitable for the study of epithelial-mesenchymal interactions in early passages when the mesenchymal component is active.

scholarly journals Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells

2015 ◽  
Vol 36 (6) ◽  
pp. 2433-2446 ◽  
Author(s):  
Siu Wai Tsang ◽  
Hong-Jie Zhang ◽  
Ye-Gao Chen ◽  
Kathy Ka-Wai Auyeung ◽  
Zhao-Xiang Bian
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Type I ◽  
Alpha Smooth Muscle Actin ◽  
Expression Levels

Background: Eruberin A (2, 3-dehydroflavonoid), a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs) is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma. Methods: The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining. Results: The application of eruberin A (20 µg/ml) effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml) stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-κB) and the phosphorylation of phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT). Conclusion: Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-κB signaling pathway.

scholarly journals Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 910
Author(s):  
Lara Testai ◽  
Vincenzo Brancaleone ◽  
Lorenzo Flori ◽  
Rosangela Montanaro ◽  
Vincenzo Calderone
Keyword(s):  
Hydrogen Sulfide ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Vascular Endothelial ◽  
Independent Manner ◽  
Mesenchymal Transition ◽  
Adult Age ◽  
Cardiovascular Fibrosis

Endothelial mesenchymal transition (EndMT) has been described as a fundamental process during embryogenesis; however, it can occur also in adult age, underlying pathological events, including fibrosis. Indeed, during EndMT, the endothelial cells lose their specific markers, such as vascular endothelial cadherin (VE-cadherin), and acquire a mesenchymal phenotype, expressing specific products, such as α-smooth muscle actin (α-SMA) and type I collagen; moreover, the integrity of the endothelium is disrupted, and cells show a migratory, invasive and proliferative phenotype. Several stimuli can trigger this transition, but transforming growth factor (TGF-β1) is considered the most relevant. EndMT can proceed in a canonical smad-dependent or non-canonical smad-independent manner and ultimately regulate gene expression of pro-fibrotic machinery. These events lead to endothelial dysfunction and atherosclerosis at the vascular level as well as myocardial hypertrophy and fibrosis. Indeed, EndMT is the mechanism which promotes the progression of cardiovascular disorders following hypertension, diabetes, heart failure and also ageing. In this scenario, hydrogen sulfide (H2S) has been widely described for its preventive properties, but its role in EndMT is poorly investigated. This review is focused on the evaluation of the putative role of H2S in the EndMT process.

Sign in / Sign up

Export Citation Format

Share Document