Defining the role of hif-1 ? And ctgf in fibrosis - biomed 2009.

Connective tissue growth factor (CTGF) plays a major role in pathways that lead to fibrosis, including fibrosis of major organs, fibroproliferative diseases, and scarring. Tissue hypoxia has been reported to induce the expression and secretion of CTGF in various tissues and organs, such as in renal cortical myofibroblasts, in renal interstitial fibroblasts, and in skin. This implicates CTGF as a mechanism of action for tissue damage caused by hypoxia. Studies have shown that cells deficient in hypoxic inducible factor 1 (HIF-1) were not able to produce CTGF mRNA, suggesting a strong association between the two proteins. In this study fibroblast cells were placed under hypoxic conditions for periods of 2, 24, 48, and 72 hours, and the levels of HIF-1, and CTGF were determined by immunocytochemical techniques. The results show a strong positive response to HIF-1 following hypoxia treatment for periods of 24 hours. By 48 and 72 hours HIF-1 levels are reduced and increases in CTGF cellular staining are noticeable. The results of our study also indicate a strong correlation between HIF-1 and CTGF. Our data also shows that once CTGF is induced, HIF-1 levels decline even though the hypoxic conditions are maintained. Determining the relationship between HIF-1 and CTGF may provide a deeper understanding of the pathogenesis of fibroproliferative disease.