Regulating factors of renal tubular hypertrophy.

Abstract

Understanding the mechanisms of tubular hypertrophy is important because these cells simply represent the bulk of the nephron, and there is a convincing link between early tubular enlargement and the progression of renal disease. It seems reasonable to assume that cytokines and polypeptide growth factors including inhibitory factors such as TGF-beta induce in concert, rather than as single factors, tubular hypertrophy. The important observations that the activation of the intrarenal renin-angiotensin axis is altered in situations associated with renal growth, and that ACE inhibitors abolish compensatory hypertrophy in many models provided for us a basis for investigating the growth effects of ANG-II on cultured proximal tubular cells. ANG-II induces, as a single factor, tubular hypertrophy in vitro, and this growth effect has been studied in detail on a molecular levels. Endogenous induction of TGF-beta by ANG-II is important in the peptide-mediated hypertrophy. While some genes induced by ANG-II, such as immediate early genes, are engaged as part of a generalized activation of the nucleus, the hypertrophic effects may be mediated by a set of novel genes which may be part of an identifiable genetic program causing tubular enlargement. The identification of hypertrophy genes may offer new insight into the modulation of cytoplasmic enlargement and its interface with elements that control the cell cycle and may provide a tool for further therapeutic interventions.