title: Inhibition of periostin expression protects against the development of renal inflammation and fibrosis.
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-β 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 periostin mediates renal disease in response to TGF-β and that blocking periostin may be a promising therapeutic strategy against the development of CKD.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale UMRS 702, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France;
authors.forename: Mouna
authors.initials: M
authors.lastname: Mael-Ainin
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale UMRS 702, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France;
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abed
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale UMRS 702, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France; Department of Physiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dussaule
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale UMRS 702, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France; christos.chatziantoniou@upmc.fr.
authors.forename: Christos
authors.initials: C
authors.lastname: Chatziantoniou
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D008297:Male; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D009400:Nephrosclerosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D050199:Podocytes / Q000502:physiology; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000502:physiology; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D016212:Transforming Growth Factor beta
keywords: Pathophysiology of Renal Disease and Progression; extracellular matrix; fibrosis; hypertension; obstructive uropathy; progression of renal failure