Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-Ã1 in vitro

Lv, Zhi‐Dong; Di, Na; Ma, Xiaoyang; Zhao, Chong; Zhao, Wenxuan; Xu, Hui

doi:10.3892/ijmm.2010.574

Cited by 20 publications

(20 citation statements)

References 17 publications

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“…TGF-β1 is also strongly associated with wound healing in general [24], [25]. ELISA was used to assess the secretion of total vs. active forms of TGF-β1 by primary mesothelial cells with and without treatment with TIMP-1-GPI or control protein.…”

Section: Resultsmentioning

confidence: 99%

“…Many factors such as TGF-β1 and TNF-α are synthesized as precursor proteins that require proteolytic processing to gain functional activity [47], [48]. TGF-β1 can effectively block the migration and proliferation of mesothelial cells [24], [25]. MMP-2 and MMP-9 activate TGF-β through proteolytic degradation of the latent TGF-β1 complex [47].…”

Section: Discussionmentioning

confidence: 99%

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Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

et al. 2012

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BackgroundMesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity.Methods and FindingBy modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1.ConclusionsTIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

et al. 2012

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“…The MKN45-P cell line has a high potential for peritoneal dissemination and could adhere to the mouse peritoneal cavity; however, injected HPMCs could not adhere to the intact peritoneal surface. HPMCs are classified as epithelial in the broadest sense of the term, and serve as a protective anatomical barrier [25]. Yashiro et al have previously demonstrated that a layer of confluent, intact mesothelial cells hindered cancer cell invasion to the abdominal cavity [16].…”

Section: Discussionmentioning

confidence: 99%

Establishing a xenograft mouse model of peritoneal dissemination of gastric cancer with organ invasion and fibrosis

et al. 2017

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BackgroundThe clinical prognosis of gastric cancer with peritoneal dissemination is poor because of its chemoresistance and rich fibrosis. While several gastric cancer cell lines have been used to establish models of peritoneal dissemination by intraperitoneal injection, most peritoneal tumors that form adopt a medullary pattern in microscopic appearance. This histological finding for the model differs from that in the clinical situation. This study was performed to demonstrate the contribution of human peritoneal mesothelial cells (HPMCs) to fibrotic tumor formation and to establish a new xenograft model with high potential for peritoneal dissemination with organ invasion and extensive fibrosis.MethodsWe established four types of xenograft model: i) intraperitoneal injection of MKN45-P cells alone (control group), ii) injection of MKN45-P cells co-cultured with HPMCs (co-cultured group), iii) scratching the parietal peritoneum (parietal group), and iv) scratching the visceral peritoneum (visceral group) with a cotton swab before injection of co-cultured cells. Fibrosis, α-smooth muscle actin expression, and organ invasion by tumor cells were all assessed by immunohistochemical examination.ResultsAll mice developed abdominal swelling with peritoneal tumors and bloody ascites. Tumors of the control and co-cultured groups were not invasive or fibrotic. Contrastingly, tumors of the scratch groups exhibited rich stromal fibrosis and possessed increased α-smooth muscle actin (α-SMA) expression. In particular, the visceral group showed edematous and spreading tumors invading the intestinal wall.ConclusionWe established a model of peritoneal dissemination with organ invasion and stromal fibrosis. Formation of peritoneal dissemination required a favorable environment for cell adhesion, invasion, and growth. This model may be useful for analyzing the pathogenesis and treatment of peritoneal dissemination of gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2991-9) contains supplementary material, which is available to authorized users.

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“…Moreover, transforming growth factor-β1 (TGF-β1) is well known as a key pro-fibrotic cytokine [15] and a key mediator of the experimental and human peritoneal fibrosis associated with PD [16]. Targeting TGF-β1 and inflammation may be a good therapeutic strategy for controlling peritoneal fibrosis and EPS.…”

Section: Introductionmentioning

confidence: 99%

Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

Zhang

et al. 2014

IJMS

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Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF.

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Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-Ã1 in vitro

Cited by 20 publications

References 17 publications

Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

Establishing a xenograft mouse model of peritoneal dissemination of gastric cancer with organ invasion and fibrosis

Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

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Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-Ã1 in vitro

Cited by 20 publications

References 17 publications

Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

Recombinant GPI-Anchored TIMP-1 Stimulates Growth and Migration of Peritoneal Mesothelial Cells

Establishing a xenograft mouse model of peritoneal dissemination of gastric cancer with organ invasion and fibrosis

Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

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Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-Ã1 in vitro