Role of up-regulation of THEM4 on extracellular matrix accumulation in kidney of diabetic mice / 中国药理学通报

ABSTRACT

Aim To observe the effect of thioesterase superfamily member 4 ( THEM4 ) expression on extra-cellular matrix ( ECM ) accumulation in the kidney of diabetic mice .Methods For in vivo vector delivery experiment , male CD1 mice were randomly divided in-to four groups normal control mice ( Control group ) , diabetic mice ( DM group ) , diabetic mice receiving pYr-ads-4-THEM4 vector ( DM+THEM4 vector ) and diabetic mice receiving pYr-adshuttle-4 vector ( DM+V vector ) .pYr-ads-4-THEM4 vector or pYr-adshuttle-4 vector ( 1 mg · kg -1 ) were mixed with TransIT-EE Hydrodynamic Delivery Solution from Mirus Co .and injected into tail vein once a week for four weeks after STZ injection.Four weeks later, mice were sacrificed and Western blot , immunohistochemistry and real-time PCR were used to detect the expression of phospho-Akt(Ser 473), THEM4, TGF-β1, α-SMA, Col Ⅲ, FN proteins and THEM4 mRNA in kidneys respectively . Results THEM4 decreased in kidney of diabetes mel-litus accompanied with increased phospho-Akt ( Ser 473), TGF-β1, α-SMA and ECM.The delivery of pYr-ads-4-THEM4 vector increased THEM4 expression and decreased phospho-Akt (Ser 473), TGF-β1, α-SMA and ECM deposit in kidneys of diabetic mice . Conclusion The up-regulation of THEM4 may pre-vent ECM deposit by inhibiting the phosphorylation of Akt and down-regulating the expression of TGF-β1 andα-SMA in kidneys of diabetic mice .