We have located links that may give you full text access.
Targeting c-fms kinase attenuates chronic aristolochic acid nephropathy in mice.
Oncotarget 2016 March 9
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some Chinese herbal medicines, but treatment remains ineffective. Macrophage accumulation is an early feature in human and experimental AAN; however, the role of macrophages in chronic AAN is unknown. We report here that targeting macrophages with fms-I, a selective inhibitor of the tyrosine kinase activity of the macrophage colony-stimulating factor receptor, suppressed disease progression in a mouse model of chronic AAN. Treatment with fms-I (10mg/kg/BID) from day 0 to 28 (prevention study) or from day 14 to 28 (intervention study) substantially inhibited macrophage accumulation and significantly improved renal dysfunction including a reduction in proteinuria and tubular damage. Progressive interstitial fibrosis (myofibroblast accumulation and collagen deposition) and renal inflammation (increased expression of MCP-1, MIF, and TNF-α) were also attenuated by fms-I treatment. These protective effects involved inhibition of TGF-β/Smad3 and NF-kB signaling. In conclusion, the present study establishes that macrophages are key inflammatory cells that exacerbates progressive tubulointerstitial damage in chronic AAN via mechanisms associated with TGF-β/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation. Targeting macrophages via a c-fms kinase inhibitor may represent a novel therapy for chronic AAN.
Full text links
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app