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Background/Aims: Since renal fibrosis always predisposes end-stage renal disease, elucidation of the molecular mechanisms that underlie the progression of renal fibrosis may substantially improve the understanding and treatment for renal failure. Previous studies have highlighted an important counteraction between transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells during chronic renal injury. Macrophages are also believed to play a critical role in renal fibrosis. However, the relationship between macrophages and EMT is unknown. Methods: Here, we used a mouse unilateral ureteral obstruction (UUO) model to address to these questions, and analyzed macrophage and its subpopulations purified by flow cytometry. Results: We found that the recruited macrophages are polarized to a M2 subtype after renal injury. M2 macrophages released high levels TGFβ1 to suppress BMP7 to enhance EMT-induced renal fibrosis. Depletion of M2 macrophages, but not of M1 macrophages, specifically inhibited EMT, and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages deteriorated renal fibrosis. Conclusion: Thus, our study highlights M2 macrophages as a critical target for treating renal fibrosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]