Transforming growth factor-β regulates tubular epithelial-myofibroblast transdifferentiation in vitro

Fan, Junming; Ng, Yee‐Yung; Hill, Prudence A.; Nikolic-Paterson, David J.; Mu, Wei; Atkins, Robert C.; Lan, Hui‐Yao

doi:10.1046/j.1523-1755.1999.00656.x

Cited by 463 publications

(419 citation statements)

References 26 publications

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“…Furthermore, TGF-β modulates the expression of integrins, which are cell-surface receptors for ECM components, thereby facilitating cell adhesion and matrix deposition [39,40]. TGF-β also acts on (myo)fibroblasts, which are the main source of the increased ECM deposition in tissue fibrosis: TGF-β is a chemoattractant for fibroblasts [41], stimulates fibroblast proliferation [42], and regulates transdifferentiation of resident kidney cells into myofibroblasts [43].…”

Section: Transforming Growth Factor-betamentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

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Section: Transforming Growth Factor-betamentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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“…In vitro stimulation of tubule epithelial cells with TGF-␤1 induced a dose dependent, high rate of myofibroblast transformation that was abolished completely by the addition of a neutralizing anti-TGF-␤1 antibody. 59 Immediately after radiation, there was a significant and dose dependent increase in the levels of TGF-␤1 and collagen mRNA in rat tubule epithelial cells. 60 In addition, the expression of protease inhibitors, which block extracellular matrix (ECM) deposition (such as plasminogen activator-inhibitor 1), also increased.…”

Section: Radiation-induced Renal Fibrosismentioning

confidence: 94%

Current concepts in radiation enteritis and implications for future clinical trials

Nguyen

Antoine

Dutta

et al. 2002

Cancer

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BACKGROUNDRadiation enteritis is one of the most feared complications of abdominal and pelvic radiation. Once its occurs, the process is relentless and may result in the patient's death. Available treatment is only supportive. Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis. New treatment modalities may be devised to improve the outcome of patients who are affected with this complication.METHODSA literature search was used to identify the common denominator between many radiation‐induced fibrotic conditions and other sclerotic diseases. Factors that affect the disease process and possible therapeutic interventions were evaluated.RESULTSThe hyperstimulation of transforming growth factor β1 (TGF‐β1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN‐γ) inhibits the effects of TGF‐β1 in the nucleus. The fibrotic process may be reverted by IFN‐γ in various pathologic conditions.CONCLUSIONSRadiation enteritis and other radiation‐induced, long‐term complications are characterized by excessive stimulation of TGF‐β1. Preliminary studies suggest that IFN‐γ may be effective in the treatment of patients with radiation‐induced cutaneous fibrosis. IFN‐γ should be considered in Phase I–II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis. Cancer 2002;95:1151–63. © 2002 American Cancer Society.DOI 10.1002/cncr.10766

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“…Submesothelial stromal cells, ovarian thecal cells, pericytes, hepatic perisinusoidal cells (hepatic stellate cells), pancreatic stellate cells or reactive macrophages have been also proposed as cells capable of expressing myofibroblastic phenotypes under pathological conditions [33][34][35][38][39][40] . Furthermore, it has been reported that renal epithelial cells may transdifferentiate into myofibroblastic cells in renal interstitial fibrosis [41][42][43][44] . It thus appears that so-called "myofibroblastic cells" in fibrotic lesions are generated from heterogeneous cell populations 45 .…”

Section: Myofibroblastsmentioning

confidence: 99%

“…2); these cytoskeletons represent useful markers of myofibroblastic differentiation 33,35 . It has been recently postulated that EMT, in which renal epithelial cells acquire myofibroblastic phenotypes, may contribute to the progressive renal fibrosis [41][42][43][44]60 . In the chronic model, it has been found that a number of cuboidal or flattened, single-or multi-layered epithelia in the fibrotic areas show a strong immunoexpression to α-SMA (Fig.…”

Section: Myofibroblasts In the Cisplatin-induced Rat Chronic Modelmentioning

confidence: 99%

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Heterogeneity of Macrophage Populations and Myofibroblasts Appearing in Rat Renal Interstitial Fibrosis

Yamate

2007

J Toxicol Pathol

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Macrophages and myofibroblasts play important roles in progressive renal fibrosis. Using cisplatin-induced rat renal fibrosis models, the author has investigated patho-biological characteristics of these cells. Macrophages seen in the fibrotic areas involve exudate macrophages, resident macrophages and antigen-presenting cells (activated dendritic cells and macrophages). In the early stages of renal fibrosis, exudate and resident macrophages are key cells for induction of myofibroblasts via producing fibrogenic factors such as transforming growth factor (TGF)-β1 and plateletderived growth factor (PDGF)-BB. In addition, these macrophages have capacity to phagocytize apoptotic bodies for clearance. [185][186][187][188][189][190][191][192][193][194][195]

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Transforming growth factor-β regulates tubular epithelial-myofibroblast transdifferentiation in vitro

Cited by 463 publications

References 26 publications

ECM homeostasis in renal diseases: a genomic approach

ECM homeostasis in renal diseases: a genomic approach

Current concepts in radiation enteritis and implications for future clinical trials

Heterogeneity of Macrophage Populations and Myofibroblasts Appearing in Rat Renal Interstitial Fibrosis

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