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《Chinese Pharmacological Bulletin》 2018-01
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Role of up-regulation of THEM4 on extracellular matrix accumulation in kidney of diabetic mice

CHEN Ning;HAO Jun;ZHU Gui-yun;AN Xiao-ying;SUN Jing-Jing;OUYANG-Qin;YANG Yong-hui;Dept of Pathology,Hebei Chest Hospital;Dept of Pathology,Hebei Medical University;  
AimTo observe the effect of thioesterase superfamily member 4(THEM4)expression on extracellular matrix(ECM)accumulation in the kidney of diabetic mice.MethodsFor in vivo vector delivery experiment,male CD1 mice were randomly divided into four groups:normal control mice(Control group),diabetic mice(DM group),diabetic mice receiving p Yr-ads-4-THEM4 vector(DM+THEM4 vector)and diabetic mice receiving p Yr-adshuttle-4 vector(DM+V vector).p Yr-ads-4-THEM4 vector or p Yr-adshuttle-4 vector(1 mg·kg~(-1))were mixed with Trans IT-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,ColⅢ,FN proteins and THEM4 mRNA in kidneys respectively.Results THEM4 decreased in kidney of diabetes mellitus accompanied with increased phospho-Akt(Ser473),TGF-β1,α-SMA and ECM.The delivery of p Yr-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.ConclusionThe up-regulation of THEM4 may prevent ECM deposit by inhibiting the phosphorylation of Akt and down-regulating the expression of TGF-β1 andα-SMA in kidneys of diabetic mice.
【Fund】: 河北省医学科学研究重点课题计划(No 20150604)
【CateGory Index】: R587.2;R692.9
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