Increased expression of epimorphin in a peritoneal fibrosis mouse model

2021 ◽  
pp. 089686082110515
Author(s):  
Muneharu Yamada ◽  
Yohei Hirai ◽  
Dan Inoue ◽  
Shuhei Komatsu ◽  
Takahiro Uchida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Real Time ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Smooth Muscle Actin ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Rt Pcr ◽  
Peritoneal Fibrosis ◽  
Compact Zone

Background: Long-term peritoneal dialysis results in functional and histopathological alterations of the peritoneal membrane, leading to peritoneal fibrosis (PF). The mechanism of PF has not been fully elucidated, and at present there is no effective therapy for PF. Epimorphin is a mesenchymal protein that not only regulates morphogenesis in organ development but is implicated in tissue repair. However, the role of epimorphin in PF has not yet been clarified. Methods: PF was induced in C57/Bl6 mice by intraperitoneal injection of chlorhexidine gluconate (CG-injected mice) three times a week for 3 weeks. The parietal peritoneum was subsequently dissected and assessed by Masson’s trichrome staining, and epimorphin expression was analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, epimorphin-positive regions were analysed by multiple immunofluorescence staining using fibrosis-associated markers. In addition, normal rat fibroblast cells (NRK-49F) were treated with transforming growth factor-β (TGF-β) in the presence or absence of epimorphin. The expression of fibrosis-associated markers was assessed by real-time RT-PCR. Results: In CG-injected mice, Masson’s trichrome staining showed marked thickening of the submesothelial compact zone. Weak epimorphin expression was observed in the narrow submesothelial compact zone beneath the mesothelial cells in control mice; however, epimorphin expression was stronger in the submesothelial compact zone in CG-injected mice. Epimorphin expression was observed mainly in α-smooth muscle actin (α-SMA)-positive myofibroblasts. Epimorphin suppressed the TGF-β-induced upregulation of α-SMA and platelet-derived growth factor receptor-β in cultured cells. Conclusions: Our results suggest that epimorphin may be a therapeutic target for fibrotic diseases of the peritoneum.

scholarly journals Characterization of human PDGFR-β-positive pericytes from IPF and non-IPF lungs

2018 ◽  
Vol 315 (6) ◽  
pp. L991-L1002 ◽  
Author(s):  
Carole L. Wilson ◽  
Sarah E. Stephenson ◽  
Jean Paul Higuero ◽  
Carol Feghali-Bostwick ◽  
Chi F. Hung ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Smooth Muscle Actin ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Marker Profile ◽  
Molecular Patterns

Pericytes are key regulators of the microvasculature through their close interactions with the endothelium. However, pericytes play additional roles in tissue homeostasis and repair, in part by transitioning into myofibroblasts. Accumulation of myofibroblasts is a hallmark of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). To understand the contribution and role of pericytes in human lung fibrosis, we isolated these cells from non-IPF control and IPF lung tissues based on expression of platelet-derived growth factor receptor-β (PDGFR-β), a common marker of pericytes. When cultured in a specialized growth medium, PDGFR-β+ cells retain the morphology and marker profile typical of pericytes. We found that IPF pericytes migrated more rapidly and invaded a basement membrane matrix more readily than control pericytes. Exposure of cells to transforming growth factor-β, a major fibrosis-inducing cytokine, increased expression of α-smooth muscle actin and extracellular matrix genes in both control and IPF pericytes. Given that pericytes are uniquely positioned in vivo to respond to danger signals of both systemic and tissue origin, we stimulated human lung pericytes with agonists having pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Both control and IPF lung pericytes increased expression of proinflammatory chemokines in response to specific PAMPs and DAMPs released from necrotic cells. Our results suggest that control and IPF lung pericytes are poised to react to tissue damage, as well as microbial and fibrotic stimuli. However, IPF pericytes are primed for migration and matrix invasion, features that may contribute to the function of these cells in lung fibrosis.

scholarly journals Delayed administration of suramin attenuates peritoneal fibrosis in rats

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chongxiang Xiong ◽  
Na Liu ◽  
Xiaofei Shao ◽  
Sairah Sharif ◽  
Hequn Zou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Effective Treatment ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Growth Factor Receptor ◽  
Peritoneal Fibrosis ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tgf Β1

Abstract Background Peritoneal fibrosis is the most common complication of peritoneal dialysis, but there is currently no effective treatment. We previously reported that suramin pretreatment prevents the development of peritoneal fibrosis in a rat model of peritoneal fibrosis induced by chlorhexidine gluconate (CG). Here, we further examined the effectiveness of delayed administration of suramin on peritoneal fibrosis and the mechanism (s) involved in this process. Methods In the rat model of peritoneal fibrosis induced by CG, suramin or saline was administered at day 21 and 28. All rats were then sacrificed to collect peritoneal tissues for Western blot analysis and histological staining at day 35. Results Our results demonstrated that delayed administration of suramin starting at 21 days following CG injection can ameliorate peritoneal damage, with greater efficacy after two injections. Suramin also reduced the expression of α-smooth muscle actin, Collagen 1, and Fibronectin and suppressed phosphorylation of Smad-3, epidermal growth factor receptor (EGFR), signal transducers, activator of transcription 3 (STAT3) as well as extracellular signal-regulated kinases 1/2 (ERK 1/2) in the peritoneum injured with CG. Moreover, delayed administration of suramin inhibited overproduction of transforming growth factor-β1(TGF-β1) and expression of several pro-inflammatory cytokines, including monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1, and interleukin-6. Conclusions Our results indicated that suramin can attenuate progression of peritoneal fibrosis by a mechanism involving inhibition of the TGF-β1/Smad3 and EGFR signaling pathways as well as suppression of multiple proinflammatory cytokines. Thus, suramin may have the potential to offer an effective treatment for peritoneal fibrosis.

scholarly journals Transforming growth factor β-induced peritoneal fibrosis is mouse strain dependent*

2012 ◽  
Vol 28 (8) ◽  
pp. 2015-2027 ◽  
Author(s):  
Peter J. Margetts ◽  
Catherine Hoff ◽  
Limin Liu ◽  
Ron Korstanje ◽  
Louise Walkin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Strain ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Peritoneal Fibrosis ◽  
Strain Dependent

Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a mouse remnant kidney model

2004 ◽  
Vol 286 (3) ◽  
pp. F516-F525 ◽  
Author(s):  
Naoko Hashimoto ◽  
Yohei Maeshima ◽  
Minoru Satoh ◽  
Masahiro Odawara ◽  
Hitoshi Sugiyama ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Glomerular Injury ◽  
Wild Mice ◽  
Angiotensin Type 2 Receptor ◽  
Glomerular Size ◽  
Nitric Oxide Metabolites

Angiotensin II mediates the progression of renal disease through the type 1 receptor (AT1R). Recent studies have suggested that type 2 receptor (AT2R)-mediated signaling inhibits cell proliferation by counteracting the actions of AT1R. The aim of the present study was to determine the effect of AT2R overexpression on glomerular injury induced by ⅚ nephrectomy (⅚Nx). AT2R transgenic mice (AT2-Tg), overexpressing AT2R under the control of α-smooth muscle actin (α-SMA) promoter, and control wild-type mice (Wild) were subjected to ⅚Nx. In AT2-Tg mice, the glomerular expression of AT2R was upregulated after ⅚Nx. Urinary albumin excretion at 12 wk after ⅚Nx was decreased by 33.7% in AT2-Tg compared with Wild mice. Glomerular size in AT2-Tg mice was significantly smaller than in Wild mice after ⅚Nx (93.1 ± 3.0 vs. 103.3 ± 1.8 μm; P < 0.05). Immunohistochemistry revealed significant decreases in glomerular expression of platelet-derived growth factor-BB chain (PDGF-BB) and transforming growth factor-β1 (TGF-β1) in AT2-Tg with ⅚Nx compared with Wild mice. Urinary excretion of nitric oxide metabolites was increased 2.5-fold in AT2-Tg compared with Wild mice. EMSA showed that activation of early growth response gene-1, which induces the transcription of PDGF-BB and TGF-β1, was decreased in AT2-Tg mice. These changes in AT2-Tg mice at 12 wk after ⅚Nx were blocked by the AT2R antagonist PD-123319. Taken together, our findings suggest that AT2R-mediated signaling may protect from glomerular injuries induced by ⅚Nx and that overexpression of AT2R may serve as a potential therapeutic strategy for glomerular disorders.

scholarly journals Gene expression of growth factor BMP15, GDF9, FGF2 and their receptors in bovine follicular cells

2018 ◽  
pp. 6778-6787 ◽  
Author(s):  
Pablo S Reineri ◽  
María S. Coria ◽  
María G. Barrionuevo ◽  
Olegario Hernández ◽  
Santiago Callejas ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Follicular Development ◽  
Fibroblast Growth ◽  
Rt Pcr ◽  
Follicular Cells

Introduction. Growth and follicular maturation involve transformations of various components of the follicle, such as the oocyte, granulosa and techa cells. Several growth factors, including differentiation growth factor 9 (GDF9), bone morphogenic protein 15 (BMP15) and basic fibroblast growth factor (FGF2) are important for follicular development and oocyte maturation, by its ability to increase the proliferation of granulosa, techa cells and the ovarian stroma. Objetive. Evaluate mRNA expression of GDF9, BMP15, FGF2 and their main receptors, transforming growth factor beta receptor 1 (TGFβ-R1), bone morphogenetic protein receptor, type IB (BMPR-IB) and fibroblast growth factor receptor 2 (FGFR2) in bovine follicular cells. Materials and methods. Total RNA was isolated from pooled samples of oocytes (OOs), cumulus cells (CCs) of cumulus oocyte complexes (COCs) and follicular cell pellets (PCs) of 70 ovaries obtained from 96 beef heifers, collected at a local abattoir. The expression pattern of growth factors and their receptors in follicular bovine cells was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Results. The mRNA transcripts encoding GDF9, BMP15, FGF2, TGFβ-R1, BMPR-IB and FGFR2 genes were detected, by RT-PCR, in all studied cells. This is the first time that the expression of TGFβ-R1 and BMPR-IB receptors is reported in bovine oocytes. Conclusions. The presence of growth factors and receptor transcripts in the studied cells indicate that these factors could act as paracrine and autocrine regulators of folliculogenesis.

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