title: Steap4 attenuates high glucose and S100B-induced effects in mesangial cells.
abstract: Six-transmembrane epithelial antigen of prostate 4 (Steap4)-knockout mice develop hyperglycaemia and inflammation whereas Steap4 overexpression attenuates atherosclerosis in diabetic mice. Thus, we studied the roles of Steap4 in high glucose (HG, 27.5 mM) or S100B (1 μM, a ligand for the receptor for advanced glycation end-product or RAGE)-induced effects in mouse mesangial (MES13) cells. We found that HG-induced Steap4 protein expression was dependent on S100B. HG increased cell membrane, but not cytosolic, Steap4 protein expression. HG increased protein-protein interaction between Steap4 and S100B, which was confirmed by mass spectrometry of immunoprecipitated S100B. SP600125, LY294002 and AG490 attenuated S100B-induced Steap4 protein expression or gene transcriptional activity. A mutation in signal transducer and activator of transcription 3 (Stat3) site 2 of the Steap4 promoter constructs resulted in a marked decrease in HG or S100B-induced activation of Steap4 gene transcription. Overexpression of Steap4 attenuates HG or S100B-induced collagen IV, fibronectin and cyclooxygenase 2 protein expression. Overexpression of Steap4 attenuates HG or S100B-induced transforming growth factor-β (TGF-β). Moreover, overexpression of Steap4 attenuates S100B-induced signalling. Finally, overexpressing Steap4 attenuated renal expression of fibronectin, S100B, TGF-β, type IV collagen, p-Akt, p-extracellular signal regulated kinase 1/2 and p-Stat3 in streptozotocin-diabetic mice. Thus, overexpression of Steap4 attenuated HG or S100B-induced effects in MES13 cells and attenuated some of S100B-induced effects in diabetic mouse kidneys.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chao-Tang
authors.initials: CT
authors.lastname: Chuang
authors.affiliation: Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yeng-Tseng
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D005353:Fibronectins; D008565:Membrane Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; D050796:STAT3 Transcription Factor; D051785:Smad Proteins; C436323:Tiarp protein, mouse; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: S100B; Steap4; high glucose; protein interaction
references.citation: Oncogene. 2005 Jul 21;24(31):4934-45
references.pmid: 15897894
references.citation: Exp Clin Endocrinol Diabetes. 2005 Jul;113(7):365-71
references.pmid: 16025396
references.citation: Cell. 2007 May 4;129(3):451-2
references.pmid: 17482536
references.citation: Cell. 2007 May 4;129(3):537-48
references.pmid: 17482547
references.citation: Nephrology (Carlton). 2007 Jun;12(3):261-6
references.pmid: 17498121
references.citation: Cell Res. 2009 Jan;19(1):58-70
references.pmid: 19050695
references.citation: FEBS Lett. 2009 Apr 2;583(7):1196-200
references.pmid: 19289123
references.citation: Biochim Biophys Acta. 2009 Jun;1793(6):1008-22
references.pmid: 19110011
references.citation: Biochim Biophys Acta. 2009 Jun;1793(6):993-1007
references.pmid: 19121341
references.citation: Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1373-84
references.pmid: 19900020
references.citation: Int J Mol Med. 2010 Mar;25(3):361-7
references.pmid: 20127040
references.citation: J Biol Chem. 2010 May 28;285(22):16453-66
references.pmid: 20304921
references.citation: Eur J Pharmacol. 2010 Sep 1;641(1):7-14
references.pmid: 20483351
references.citation: Diabetes. 2011 Mar;60(3):1019-29
references.pmid: 21266331
references.citation: J Biol Chem. 2011 Mar 4;286(9):7214-26
references.pmid: 21209080
references.citation: Nat Rev Nephrol. 2011 Jun;7(6):327-40
references.pmid: 21537349
references.citation: Antioxid Redox Signal. 2011 Jul 1;15(1):205-18
references.pmid: 21050144
references.citation: J Recept Signal Transduct Res. 2011 Oct;31(5):332-9
references.pmid: 21929288
references.citation: Mol Cancer Res. 2012 May;10(5):573-87
references.pmid: 22522456
references.citation: Proteomics. 2012 May;12(10):1576-90
references.pmid: 22611051
references.citation: Vascul Pharmacol. 2012 Nov-Dec;57(5-6):160-7
references.pmid: 22750165
references.citation: Am J Pathol. 2012 Dec;181(6):1991-2002
references.pmid: 23041393
references.citation: IUBMB Life. 2013 Jan;65(1):9-16
references.pmid: 23281033
references.citation: Int J Biochem Cell Biol. 2013 Mar;45(3):612-20
references.pmid: 23262293
references.citation: J Proteomics. 2013 Apr 9;81:91-101
references.pmid: 23153790
references.citation: Proteomics. 2013 Apr;13(7):1164-79
references.pmid: 23349036
references.citation: PLoS One. 2013;8(11):e78903
references.pmid: 24236066
references.citation: Int J Biol Sci. 2014;10(3):321-6
references.pmid: 24643198
references.citation: J Cell Mol Med. 2014 Apr;18(4):735-48
references.pmid: 24467451
references.citation: Diabetologia. 2000 May;43(5):649-59
references.pmid: 10855540
references.citation: Am J Kidney Dis. 2004 Apr;43(4):636-50
references.pmid: 15042541
references.citation: Diabetes. 2004 Apr;53(4):1119-27
references.pmid: 15047630
references.citation: Diabetologia. 2004 May;47(5):844-52
references.pmid: 15127201
references.citation: J Am Soc Nephrol. 2004 Oct;15(10):2637-47
references.pmid: 15466268
references.citation: Cell. 1992 Dec 11;71(6):1003-14
references.pmid: 1333888
references.citation: J Virol. 1994 Sep;68(9):5730-7
references.pmid: 8057454
references.citation: Am J Physiol. 1996 Dec;271(6 Pt 2):F1202-10
references.pmid: 8997394
references.citation: Biol Cell. 2005 May;97(5):339-47
references.pmid: 15836432
references.citation: J Biol Chem. 2006 May 12;281(19):13685-93
references.pmid: 16551628