| 초록 |
Objectives: Inhibitors of protein tyrosine kinases(PTP) has been investigated as potential anti-fibrotic agents. PTP4A1 belongs to a sub-class of three prenylated PTP. PTP4A1 has known as promoting growth and migration of tumor cells. The role PTP4A1 has little known in kidney. We evaluated whether the PTP4A1 could be target of renal fibrosis.
Methods: 10 week old male background PTP4A1 KO mice and wild type mice were divided into 4 groups; wild, PTP4A1 KO, wild with UUO, and PTP4A1 KO with UUO. Mice were sacrificed at 7 days after surgery and kidney tissue were collected. Molecular study and Histologic examination were performed.
Results: PTP4A1 KO with UUO mice showed decrease of renal tubule-interstitial damage and fibrosis compared to wild type UUO mice. PTP4A1 KO with UUO reduced the renal expression of α-SMA and TGF-β in UUO kidney, compared to wild type with UUO mice. Wild type with UUO kidney showed decrease of renal expression of E-cadherin, compared to sham mice. However, PTP4A1 KO UUO showed increase of renal expression of E-cadherin, compared to Wild type UUO mice. In vitro, silencing of PTP4A1 in TGF-β treated HK2 cell showed increase of E-cadherin and decrease of hosphorylation of AKT and GSK3ß
Conclusions: PTP4A1 KO ameliorate renal fibrosis in UUO kidney.
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