title: Steroidogenic acute regulatory-related lipid transfer domain protein 5 localization and regulation in renal tubules.
abstract: STARD5 is a cytosolic sterol transport protein that is predominantly expressed in liver and kidney. This study provides the first report on STARD5 protein expression and distribution in mouse kidney. Immunohistochemical analysis of C57BL/6J mouse kidney sections revealed that STARD5 is expressed in tubular cells within the renal cortex and medullar regions with no detectable staining within the glomeruli. Within the epithelial cells of proximal renal tubules, STARD5 is present in the cytoplasm with high staining intensity along the apical brush-border membrane. Transmission electron microscopy of a renal proximal tubule revealed STARD5 is abundant at the basal domain of the microvilli and localizes mainly in the rough endoplasmic reticulum (ER) with undetectable staining in the Golgi apparatus and mitochondria. Confocal microscopy of STARD5 distribution in HK-2 human proximal tubule cells showed a diffuse punctuate pattern that is distinct from the early endosome marker EEA1 but similar to the ER membrane marker GRP78. Treatment of HK-2 cells with inducers of ER stress increased STARD5 mRNA expression and resulted in redistribution of STARD5 protein to the perinuclear and cell periphery regions. Since recent reports show elevated ER stress response gene expression and increased lipid levels in kidneys from diabetic rodent models, we tested STARD5 and cholesterol levels in kidneys from the OVE26 type I diabetic mouse model. Stard5 mRNA and protein levels are increased 2.8- and 1.5-fold, respectively, in OVE26 diabetic kidneys relative to FVB control kidneys. Renal free cholesterol levels are 44% elevated in the OVE26 mice. Together, our data support STARD5 functioning in kidney, specifically within proximal tubule cells, and suggest a role in ER-associated cholesterol transport.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville 40202, USA.
authors.forename: Yu-Chyu
authors.initials: YC
authors.lastname: Chen
authors.forename: Renate K
authors.initials: RK
authors.lastname: Meier
authors.forename: Shirong
authors.initials: S
authors.lastname: Zheng
authors.forename: Syed J
authors.initials: SJ
authors.lastname: Khundmiri
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tseng
authors.forename: Eleanor D
authors.initials: ED
authors.lastname: Lederer
authors.forename: Paul N
authors.initials: PN
authors.lastname: Epstein
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Clark
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001692:Biological Transport; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002147:Calmodulin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C456546:STARD5 protein, human; C499212:Stard5 protein, mouse; D002784:Cholesterol