Urine derived stem cell ameliorates renal fibrosis via klotho activation

Abstract Background and Aims After renal IRI, regeneration and recovery of the renal tubular cell occurs. However, if the renal repair process is maladaptive, it progresses to renal fibrosis. The role of stem cells in kidney regeneration or fibrosis has not been fully elucidated. we evaluated the urine drived stem cells (UDSC) for renal inflammation and fibrosis after renal ischemia reperfusion (IR). Method 10 week old balb/c nude male mice were used. sham, sham with UDSC, IR, IR with UDSC. UDSC were infused 3 times via tail vain at 6, 7, 8th day after renal IR. Urine NGAL/creatinine (Cr) were checked. The kidneys tissue were harvested at day 14 day. In vitro, TGF-β treated HK2 cell were co-cultured with UDSC. Klotho siRNA silencing was performed in UDSC. Results Urinary NGAL/Cr were significantly increased in IR mice after 14 day IR, compared to sham mice. Urinary NGAL/Cr significantly decreased in UDSC treated IR mice, compared to IR mice. In H&E stain, renal tubulo-interstitial injury were significantly decreased in UDSC treated IR mice, compared to IR mice. In masson trichrom stain, renal fibrosis area were were significantly decreased in UDSC treated IR mice, compared to IR mice. The renal expression of TGF-β, α-SMA, and collagne IV were significantly decreased in UDSC treated IR mice, compared to IR mice. The renal expression of Klotho were increased in UDSC treated IR mice, compared to IR mice. in vitro, UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-β in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-β-inhibiting ability of UDSCs. Conclusion UDSC attenuate renal fibrosis after renal IR. Klotho-secretion of UDSC play a role in these anti- fibrotic effects.