Tubular expression of heat-shock protein 27 inhibits fibrogenesis in obstructive nephropathy

Aparna Vidyasagar, Shannon R. Reese, Omeed Hafez, Ling Jin Huang, William F. Swain, Lynn M. Jacobson, Jose R. Torrealba, Pierre Emmanuel Chammas, Nancy A. Wilson, Arjang Djamali

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Morphological changes that occur during kidney injury involve actin skeleton remodeling. Here we tested whether heat-shock protein 27 (HSP27), a small stress response protein involved in cytoskeletal remodeling, protects the kidney from tubulointerstitial fibrosis in obstructive nephropathy. Tubular cell HSP27 immunostaining was significantly increased in human kidneys with ureteropelvic junction obstruction, supporting the clinical relevance of our studies. To develop an animal model for mechanistic studies, we generated transgenic mice that specifically overexpress human HSP27 in renal tubules, under the kidney androgen-regulated protein promoter, and determined the effects of HSP27 overexpression on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis following unilateral ureteral obstruction. This was associated with decreased fibrogenesis as evidenced by significant declines in phosphorylated p38MAPK, collagen III, α-smooth muscle actin, 4-hydroxynonenal, and reduced trichrome staining following obstruction. Notably, E-cadherin and β-catenin remained at the cell membrane of tubular cells in transgenic mice with an obstructed ureter. Monocyte/macrophage infiltration, however, was not significantly affected in these transgenic mice. Thus, tubular HSP27 inhibits fibrogenesis in obstructive nephropathy. Further studies are needed to determine pathways regulating the interactions between HSP27 and the E-cadherin-β-catenin complex.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalKidney international
Volume83
Issue number1
DOIs
StatePublished - Jan 2013

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Keywords

  • HSP27
  • fibrosis
  • unilateral ureteral obstruction

ASJC Scopus subject areas

  • Nephrology

Cite this

Vidyasagar, A., Reese, S. R., Hafez, O., Huang, L. J., Swain, W. F., Jacobson, L. M., Torrealba, J. R., Chammas, P. E., Wilson, N. A., & Djamali, A. (2013). Tubular expression of heat-shock protein 27 inhibits fibrogenesis in obstructive nephropathy. Kidney international, 83(1), 84-92. https://doi.org/10.1038/ki.2012.336