title: S100B is required for high glucose-induced pro-fibrotic gene expression and hypertrophy in mesangial cells.
abstract: The advanced glycation end‑product (AGE)‑receptor for AGE (RAGE) axis induces transforming growth factor‑β (TGF‑β) expression, cell hypertrophy and increases extracellular matrices that are indicated in the pathogenesis of diabetic nephropathy (DN). RAGE binds to numerous ligands besides AGE, including S100B. In the present study, the roles of S100B in high glucose‑induced p21WAF1, extracellular matrices, TGF‑βl and cell hypertrophy in mouse mesangial (MES13) cells were investigated. High glucose (30 mM) time‑dependently (24‑72 h) induced S100B expression. High glucose and exogenous S100B (1 µM) time‑dependently increased p21WAF1 gene transcription and protein expression, increased type IV collagen and fibronectin protein expression, and TGF‑β gene transcription and bioactivity. Exogenous S100B also time‑dependently activated the extracellular regulated kinases (ERK1/2), p38 kinase and c‑Jun N‑terminal kinase (JNK) signaling pathways. Exogenous S100B‑induced TGF‑β gene transcription and bioactivity were attenuated by SB203580 (p38 kinase inhibitor) and PD98059 (ERK1/2 inhibitor). Finally, the knockdown of S100B by small interfering RNA (siRNA) attenuated high glucose‑induced TGF‑β gene transcription and bioactivity, type IV collagen and fibronectin protein expression and p21WAF1 protein expression. Thus, S100B induced TGF‑β via the ERK1/2 and p38 kinase pathways in mesangial cells. Additionally, high glucose‑induced pro‑fibrotic genes (TGF‑β, type IV collagen and fibronectin) and cell hypertrophy‑related p21WAF1 are dependent on S100B.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Chao-Tang
authors.initials: CT
authors.lastname: Chuang
authors.affiliation: Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
mesh_terms: D000818:Animals; D002460:Cell Line; D024141:Collagen Type IV / Q000096:biosynthesis / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: C493957:Cdkn1a protein, mouse; D024141:Collagen Type IV; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005353:Fibronectins; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; D013549:Sweetening Agents; D016212:Transforming Growth Factor beta; D005947:Glucose