BACKGROUND/AIMS: Renal artery stenosis (RAS), which may lead to renal fibrosis, is a common cause of end-stage renal disease in elderly patients. However, the potential mechanisms leading to the development of renal fibrosis and atrophy have not been clarified. METHODS: A two-kidney, one-clip Goldblatt mouse model was established in the present study. Blood pressure, morphological and pathological alterations were examined on days 7, 14, and 28 after surgery. Peritubular capillary loss and pericyte changes after injury were evaluated. Inflammatory macrophage infiltration and Wnt/β-catenin signaling were also investigated. RESULTS: A significant increase in blood pressure and obvious renal atrophy were observed on days 7, 14, and 28 after surgery. Following surgery, the clipped kidneys developed aggravated interstitial fibrosis and tubular epithelial injury over time. Moreover, RAS induced obvious peritubular capillary loss and inflammatory macrophage infiltration. Increased pericyte number was found in the clipped kidneys, but these cells detached from the endothelial cells and migrated to the interstitium. Wnt/β-catenin signaling was also significantly upregulated in the clipped kidneys after surgery. CONCLUSION: Our study provides a novel insight into the mechanisms linking peritubular capillary loss and pericyte changes in RAS-induced renal fibrosis. Our findings also suggest that inflammatory macrophages and Wnt/β-catenin signaling participate in these pathological processes. Therefore, multi-target therapeutic strategies may significantly contribute to the prevention of renal interstitial fibrosis and the preservation of renal function in patients with RAS.
BACKGROUND/AIMS: Renal artery stenosis (RAS), which may lead to renal fibrosis, is a common cause of end-stage renal disease in elderly patients. However, the potential mechanisms leading to the development of renal fibrosis and atrophy have not been clarified. METHODS: A two-kidney, one-clip Goldblatt mouse model was established in the present study. Blood pressure, morphological and pathological alterations were examined on days 7, 14, and 28 after surgery. Peritubular capillary loss and pericyte changes after injury were evaluated. Inflammatory macrophage infiltration and Wnt/β-catenin signaling were also investigated. RESULTS: A significant increase in blood pressure and obvious renal atrophy were observed on days 7, 14, and 28 after surgery. Following surgery, the clipped kidneys developed aggravated interstitial fibrosis and tubular epithelial injury over time. Moreover, RAS induced obvious peritubular capillary loss and inflammatory macrophage infiltration. Increased pericyte number was found in the clipped kidneys, but these cells detached from the endothelial cells and migrated to the interstitium. Wnt/β-catenin signaling was also significantly upregulated in the clipped kidneys after surgery. CONCLUSION: Our study provides a novel insight into the mechanisms linking peritubular capillary loss and pericyte changes in RAS-induced renal fibrosis. Our findings also suggest that inflammatory macrophages and Wnt/β-catenin signaling participate in these pathological processes. Therefore, multi-target therapeutic strategies may significantly contribute to the prevention of renal interstitial fibrosis and the preservation of renal function in patients with RAS.
Authors: Nattawat Klomjit; Xiang-Yang Zhu; Alfonso Eirin; Aditya S Pawar; Sabena M Conley; Amrutesh S Puranik; Christopher M Ferguson; Seo Rin Kim; Hui Tang; Kyra L Jordan; Ishran M Saadiq; Amir Lerman; Joseph P Grande; Stephen C Textor; Lilach O Lerman Journal: Nephrol Dial Transplant Date: 2022-09-22 Impact factor: 7.186