Role of expression of endothelin-1 and angiotensin-II and hypoxia-inducible factor-1α in the kidney tissues of patients with diabetic nephropathy.

The objective of this study was to detect the expression of Angiotensin-II (Ang-II), Hypoxia-inducible factor-1α (HIF-1α) and Endothelin-1 (ET-1) in the kidneys of patients with diabetic nephropathy (DN) and to investigate their relationship with renal interstitial fibrosis (RIF). A total of 47 paraffin specimens of patients with DN and six controls were enrolled in this study, and all were diagnosed by histopathology. We studied the expressions of Ang-II, HIF-1α and ET-1 by immuno-histochemical staining and the level of RIF by Masson staining. The following results were found: (a) RIF existed in the kidneys of patients with DN, (b) the expressions of Ang-II, HIF-1α and ET-1 were lower in the control group but increased significantly in the DN group, (c) the expression of Ang-II, HIF-1α and ET-1 in tubular epithelial cells directly correlated with RIF (r s = 0.659, 0.633, 0.716, P <0.01) and (d) the expression of Ang-II, ET-1 and HIF-1α in the kidneys of patients with DN positively correlated with serum creatinine (Scr) levels (r s = 0.391, 0.594, 0.531, P <0.01) but they did not correlate with the 24-h urinary protein, blood glucose and serum albumin levels. These results provide new insights suggesting that over-expression of Ang-II, HIF-1α and ET-1 promote the progression of RIF in DN. Thus, targeting reduction in the expression of Ang-II, HIF-1α and ET-1 can delay RIF in DN. Further studies are needed to validate this observation.