Glomeruiar Expression of Hydrogen Peroxide-Inducible Cione-5 in Hyman and Rat Progressiwe Mesangial Proliferatiwe Glomerulonephritis

摘要

Background/Aims: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-beta_1 (TGF-beta_1)- and hydrogen peroxide (H_2O_2)-inducible focal adhesion protein that may be necessary for maintaining the myofibroblastic phenotype in pathological scar formation. To investigate the involvement of Hic-5 in the pathogenesis of glomerulonephritis (GN), we examined the glomeruiar expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-beta_1 in vitro. Methods and Results: Immunohistochemical analyses showed that the expression of Hic-5 was increased in mesangial cells (MCs) in human mesangial proliferative GN. Hic-5 expression was significantly correlated not only with the levels of alpha-smooth muscle actin (alpha-SMA) and TGF-beta_1 the accumulation of extracellular matrix, and the number of glomeruiar cells, but also with the urinary protein level in patients with GN. Glomeruiar Hic-5 expression increased in parallel with a-SMA expression in a rat model of mesangial proliferative GN. Combined therapy with an angiotensin type I receptor blocker and an antioxidant in this model improved the histology and the expression of Hic-5 and a-SMA. TGF-beta_1 upregulated Hic-5 and a-SMA protein levels in human cultured MCs. Conclusion: Our findings suggest that Hic-5 is involved in changes in the MC phenotype to produce abnormal extracellular matrix remodeling in GN.