Role of impaired peritubular capillary and hypoxia in progressive interstitial fibrosis after 56 subtotal nephrectomy of rats

Abstract

To investigate the potential role of peritubular capillary (PTC) loss and subsequent hypoxia as a pathogenic factor in interstitial fibrosis after renal ablation in rats. PTC loss and tubulointerstitial hypoxia in remnant kidney rats (SNTx group), sham-operated rats (sham group) and normal animals (normal group) were assessed by peritubular CD141-positive staining lumina and tubulointerstitial hypoxia-inducible factor alpha subunit 1 (HIF-1alpha) expression, respectively, at the time points of week 3, week 6 and week 12. The related cardinal factors contributing to interstitial fibrosis, such as transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) were also evaluated and analysed in the context of progressive PTC loss. Expression of TGF-beta1 mRNA in cultured renal tubular epithelial cells (MDCK cells) exposed to hypoxia was also investigated. PTC loss and tubulointerstitial hypoxia were noted even in the early stage (week 3) when the interstitial fibrosis was mild, and were persistent in the process of developing interstitial fibrosis. An in vitro study showed that hypoxia enhanced TGF-beta1 mRNA expression in the MDCK cells. PTC loss or hypoxic milieu in the tubulointerstitium is a pathological event, which may contribute to the developing interstitial fibrosis mediated by direct hypoxic effects and via hypoxia-induced TGF-beta1 expression.