4161 DELETION OF PROTEIN TYROSINE KINASES 4A1 AMELIORATE RENAL FIBROSIS INDUCED BY UUO IN MICE

Abstract Background and Aims Inhibitors of protein tyrosine kinases has been investigated as potential anti-fibrotic agents. protein tyrosine kinases 4A1 belongs to a sub-class of three prenylated protein tyrosine kinases. protein tyrosine kinases 4A1 has known as promoting growth and migration of tumor cells. The role protein tyrosine kinases 4A1 has little known in kidney. We evaluated whether the protein tyrosine kinases 4A1 could be target of renal fibrosis. Method 10 weeks old male background protein tyrosine kinases 4A1 KO mice and wild type mice were divided into 4 groups; wild, protein tyrosine kinases 4A1 KO, wild with unilateral ureteral obstruction, and protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction. Mice were sacrificed at 7 days after surgery and kidney tissue were collected. Molecular study and Histologic examination were performed. Results Protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction mice showed decrease of renal tubule-interstitial damage and fibrosis compared to wild type unilateral ureteral obstruction mice. protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction reduced the renal expression of α-SMA and TGF-β in unilateral ureteral obstruction kidney, compared to wild type with unilateral ureteral obstruction mice. Wild type with unilateral ureteral obstruction kidney showed decrease of renal expression of E-cadherin, compared to sham mice. However, protein tyrosine kinases 4A1 KO unilateral ureteral obstruction showed increase of renal expression of E-cadherin, compared to Wild type unilateral ureteral obstruction mice. In vitro, silencing of protein tyrosine kinases 4A1 in TGF-β treated HK2 cell showed increase of E-cadherin and decrease of phosphorylation of AKT and GSK3ß. Conclusion Protein tyrosine kinases 4A1 KO ameliorate renal fibrosis in unilateral ureteral obstruction kidney.