Expression of apoptosis-related genes and proteins in experimental chronic renal scarring

B. Yang, T. S. Johnson, G. L. Thomas, P. F. Watson, B. Wagner, N. J. Skill, J. L. Haylor, A. M. El Nahas

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Apoptosis has been proposed to play an important role in the progression of renal scarring. The mechanisms that determine whether a cell enters the apoptotic program are complex. Bax and Bcl-2 are recognized modulators of this event; their relative levels determine the fate of cells. A role for apoptosis in the progression of renal scarring in the remnant kidneys of rats submitted to subtotal nephrectomy (SNx) has been described. This study investigated the expression (protein and mRNA) of Bax and Bcl-2 in remnant kidneys between day 7 and day 120 post-SNx. Northern blot analysis showed that bax mRNA was increased in remnant kidneys from day 7 (150% of control; P < 0.05), whereas bcl-2 mRNA was decreased from day 15 (23% of control; P < 0.05) resulting in a 14-fold increase in the ratio of bax to bcl-2 mRNA by day 120. Western blot analysis showed similar changes in Bax and Bcl-2 protein in remnant kidneys, resulting in a 147-fold increase in the ratio of Bax to Bcl-2 on day 120. Immunohistochemistry showed increases in Bax to be located predominantly in tubules in SNx kidneys. Interestingly, Bcl-2 immunostaining increased in some epithelial cells within atrophic tubules despite the overall decrease in Bcl-2 protein and mRNA. The overall renal apoptotic cells correlated closely with the ratio of bax to bcl-2 at both the mRNA and protein levels (r = 0.594 and 0.308, respectively; P < 0.05). Furthermore, tubular apoptosis correlated positively with the mRNA level of bax (r = 0.471; P < 0.01) and negatively with the mRNA and protein levels of bcl-2 (r = -0.443 and -0.607, respectively; P < 0.01). The increase in the ratio of the death inducer (Bax) to the death repressor (Bcl-2) at the mRNA and protein levels may control the apoptosis associated with the progression of tubular atrophy and chronic renal fibrosis within remnant rat kidneys. These observations may have prognostic and therapeutic implications in chronic renal failure.

Original languageEnglish (US)
Pages (from-to)275-288
Number of pages14
JournalJournal of the American Society of Nephrology
Volume12
Issue number2
StatePublished - Feb 14 2001
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Yang, B., Johnson, T. S., Thomas, G. L., Watson, P. F., Wagner, B., Skill, N. J., Haylor, J. L., & El Nahas, A. M. (2001). Expression of apoptosis-related genes and proteins in experimental chronic renal scarring. Journal of the American Society of Nephrology, 12(2), 275-288.