Inhibition of periostin expression protects against the development of renal inflammation and fibrosis

Mouna Mael-Ainin, Ahmed Abed, Simon J. Conway, Jean Claude Dussaule, Christos Chatziantoniou

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/ or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-b to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME-induced renal injury. These data strongly suggest that periostinmediates renal disease in response to TGF-b and that blocking periostinmay be a promising therapeutic strategy against the development of CKD.

Original languageEnglish (US)
Pages (from-to)1724-1736
Number of pages13
JournalJournal of the American Society of Nephrology
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2014

ASJC Scopus subject areas

  • Nephrology

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