Glomerular expression of hydrogen peroxide-inducible clone-5 in human and rat progressive mesangial proliferative glomerulonephritis.

BACKGROUND/AIMS: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-β(1) (TGF-β(1))- and hydrogen peroxide (H(2)O(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 glomerular expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-β(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 α-smooth muscle actin (α-SMA) and TGF-β(1), the accumulation of extracellular matrix, and the number of glomerular cells, but also with the urinary protein level in patients with GN. Glomerular Hic-5 expression increased in parallel with α-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 α-SMA. TGF-β(1) upregulated Hic-5 and α-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.