Korean J Transplant.  2022 Nov;36(Supple 1):S166. 10.4285/ATW2022.F-2903.

Urine-derived stem cell attenuated renal fibrosis via Klotho activation

• Shin JA
• Lee EJ
• Ham YR
• Kim HR
• Jeon JW
• Lee KW
• Na KR
• Choi DE

• KMID: 2535682
• DOI: http://doi.org/10.4285/ATW2022.F-2903

Abstract

Background
After renal ischemia reperfusion injury (IR), 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 derived stem cells (UDSC) for renal inflammation and fibrosis after renal IR.
Methods
10-week-old balb/c nude male mice were used. Sham, sham with UDSC, IR, IR with UDSC. UDSC were infused three 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. In vitro, TGF- 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 sig-nificantly decreased in UDSC treated IR mice, compared to IR mice. In Masson trichrome stain, renal fibrosis area were sig-nificantly decreased in UDSC treated IR mice, compared to IR mice. The renal expression of MCP-1, osteopontin, TGF-beta, alpha-SMA, collagen IV, and F4/80 positive cells 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 TGF-beta in HK-2 human renal proximal tubule cells in an in vitro model. Klotho-siRNA silencing reduced the TGF-beta-inhibiting ability of UDSCs.
Conclusions
UDSC attenuate renal fibrosis after renal IR. Klotho-secretion of UDSC play a role in these anti-fibrotic effects.