Biomedical subjects

Zhi Gang Zhang

Publications and source records attributed to Zhi Gang Zhang.

2 recordsLinked to original sources

PubMed2006

Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic change induced by transforming growth factor-beta1.

Prohibitin (PHB), a potential tumor suppressor, has been shown to inhibit cell proliferation by repressing E2F-mediated transcription. But little is known about the role of PHB involved in tubulointerstitial fibrosis (TIF). Here, for the first time, we found PHB protein was positively expressed at normal renal tissues, strongly down-regulated in renal biopsy specimens, and negatively correlated with the expression of alpha-smooth-muscle actin (alpha-SMA) and with the degrees of tubulointerstitial lesions. Transforming growth factor-beta1 (TGF-beta1) is the most important profibrotic cytokine in the process of TIF and capable of inducing cell phenotypic change of interstitial fibroblasts characterized by the de novo expression of alpha-SMA. Confocal microscopy showed majority of PHB is located at cytoplasm as well as at nucleus in rat kidney fibroblasts cell (NRK-49F). As we found that PHB protein and mRNA expression were down-regulated in NRK-49F cells following TGF-beta1 stimulation. We used transient transfection to over-express PHB protein and found that cells with increased PHB levels had a significant reduction in the percentage entering cell cycle and abolished de novo expression of alpha-SMA following TGF-beta1 stimulation. Therefore, over-expression of PHB suppresses renal interstitial fibroblasts proliferation and cell phenotypic change induced by TGF-beta1, which indicates PHB as a potential therapeutic target to halt the progression of TIF.

Actins↗

PubMed2006

Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions.

The extracellular matrix (ECM) environment in connective tissues provides fibroblasts with a structural scaffold and modulates cell shape, but it also profoundly influences the fibroblast phenotype. Here we studied fibroblasts cultured in a three-dimensional network of native collagen, which was either mechanically stressed or relaxed. Mechanical load induces fibroblasts that synthesize abundant ECM and a characteristic array of cytokines/chemokines. This phenotype is reminiscent of late granulation tissue or scleroderma fibroblasts. By contrast, relaxed fibroblasts are characterized by induction of proteases and a subset of cytokines that does not overlap with that of mechanically stimulated cells. Thus, the biochemical composition and physical nature of the ECM exert powerful control over the phenotypes of fibroblasts, ranging from "synthetic" to "inflammatory" phenotypes. Interactions between fibroblasts and collagen fibrils are mostly mediated by a subset of beta 1 integrin receptors. Fibroblasts utilize alpha 1 beta 1, alpha 2 beta 1, and alpha 11 beta 1 integrins for establishing collagen contacts and transducing signals. In vitro assays and mouse genetics have demonstrated individual tasks served by each receptor, but also functional redundancy. Unraveling the integrated functions of fibroblasts, collagen integrin receptors, collagen fibrils, and mechanical tension will be important to understand the molecular mechanisms underlying tissue repair and fibrosis.

Animals↗