Presentation Authors: Wei Zhu*, Guohua Zeng, Guangzhou, China, People's Republic of, Chawnshang Chang, Rochester, NY
Introduction: Gender disparity may play key roles for the development of calcium oxalate (CaOx) kidney stones, and renal macrophages may influence the CaOx crystals deposits. The detailed mechanisms, however, remains unclear. Here we investigate the impact of androgen receptor (AR) through altering the infiltrating macrophages to influence the kidney stone formation.
Methods: In the in vitro study, we knocked down the AR in renal tubular HK-2 or HK-8 cells, and detected the renal cell capacity to recruit THP-1 macrophages after CaOx crystals exposure. The phagocytic ability and the M2 markers expression of the recruited THP-1 macrophages were also examined. In the in vivo study, we established the AR knockout mice with selectively knocked out AR in renal tubular epithelial cells. The mice were with injected with glyoxylate to induce CaOx formation. Renal crystal deposits and expression of macrophages-related proteins was examined by Pizzolato method and immunohistochemistry, respectively.
Results: Knocking down the AR in renal tubular HK-2 or HK-8 cells increased these renal cells capacity to recruit THP-1 macrophages, and promoted these infiltrated macrophages differentiationed toward the anti-inflammatory M2 phenotype that might then lead to enhancing the phagocytosis of CaOx crystals. Mice with selectively knocked out AR in renal tubular epithelial cells in the Cre-loxP mice to selectively knocked out AR in renal tubular epithelial cells also demonstrated that mice lacking AR in renal tubular epithelial cells had reduced CaOx crystals deposition with more recruited anti-inflammatory M2 macrophages in the kidney compared to the wild type control mice.
Conclusions: AR may function via altering the infiltrating M2 macrophages to influence the CaOx crystals deposition.