OBJECTIVE: To investigate the effects of poly(ADP-ribose) polymerase-1 (PARP-1) on angiotensin II (Ang II)-induced plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) in rat mesangial cells (RMCs). METHODS: Followed by serum starvation for 16 h, RMCs were exposed to Ang II for an indicated time to examine the protein expression of PARP-1. The cells were treated with or without Ang II for 12-24 h in the presence or absence of an inhibitor of PARP, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride (PJ34) or small interfering RNA (siRNA) duplexes targeting PARP-1. The mRNA and protein expressions of PARP-1, PAI-1 and FN were determined by real-time RT-PCR and Western blot, respectively. The activity of PARP-1 was examined by colorimetric assay. RESULTS: Ang II did not only significantly induce PARP-1 expression and activity, but also increased PAI-1 and FN expression in RMCs. All these responses induced by Ang II were significantly inhibited by both the PARP inhibitor PJ34 and downregulating PARP-1 with the siRNA technique. CONCLUSIONS: Our data suggest that PARP-1 mediates Ang II-induced PAI-1 and FN in RMCs and may thus represent a potential therapeutic target in the treatment of glomerular disease.
OBJECTIVE: To investigate the effects of poly(ADP-ribose) polymerase-1 (PARP-1) on angiotensin II (Ang II)-induced plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) in rat mesangial cells (RMCs). METHODS: Followed by serum starvation for 16 h, RMCs were exposed to Ang II for an indicated time to examine the protein expression of PARP-1. The cells were treated with or without Ang II for 12-24 h in the presence or absence of an inhibitor of PARP, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride (PJ34) or small interfering RNA (siRNA) duplexes targeting PARP-1. The mRNA and protein expressions of PARP-1, PAI-1 and FN were determined by real-time RT-PCR and Western blot, respectively. The activity of PARP-1 was examined by colorimetric assay. RESULTS:Ang II did not only significantly induce PARP-1 expression and activity, but also increased PAI-1 and FN expression in RMCs. All these responses induced by Ang II were significantly inhibited by both the PARP inhibitor PJ34 and downregulating PARP-1 with the siRNA technique. CONCLUSIONS: Our data suggest that PARP-1 mediates Ang II-induced PAI-1 and FN in RMCs and may thus represent a potential therapeutic target in the treatment of glomerular disease.
Authors: Brendan Gongol; Traci Marin; I-Chen Peng; Brian Woo; Marcy Martin; Stephanie King; Wei Sun; David A Johnson; Shu Chien; John Y-J Shyy Journal: Proc Natl Acad Sci U S A Date: 2013-02-04 Impact factor: 11.205