Poly(ADP‐ribose) Polymerase‐1 Deficiency Attenuates Renal Inflammation and Fibrosis in Obstructive Nephropathy

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) activation contributes to necrotic cell death and inflammation in several disease models; however, the role of PARP‐1 in a fibrotic disease remains to be defined. In this study, we tested whether PARP‐1 is involved in the pathogenesis of renal fibrosis using unilateral ureteral obstruction (UUO) mouse model. UUO was performed by ligation of the left ureter near the renal pelvis in PARP‐1 wild‐type (WT) and knockout (KO) male mice. After 10 days of UUO, renal PARP‐1 expression and activation were strongly increased by 6‐ and 13‐fold, respectively. Interstitial fibrosis induced by UUO was significantly attenuated in PARP‐1 KO mice compared to that in PARP‐1 WT mice kidneys, based on the collagen deposition (Sirius Red staining and hydroxyproline level) and the expression of myofibroblast markers (α‐smooth muscle actin and fibronectin). The UUO kidneys in PARP‐1 KO mice also showed less induction of pro‐inflammtory proteins (intercellular adhesion molecule‐1, tumor necrosis factor‐α, inducible nitric oxide synthase, and toll‐like receptor‐4) and infiltration of inflammatory cells (neutrophil and macrophage) than that in PARP‐1 WT mice. These data demonstrate that PARP‐1 activation promote renal fibrosis via activation of inflammatory signaling pathways in the UUO mouse model. (Funding source: UNMC departmental funds)