title: Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro.
abstract: Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Mengsi
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Obstetrics and Gynecology, Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Pathology, Medical School of Shandong University, Jinan 250012, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhen
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Jiangong
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002465:Cell Movement; D005947:Glucose / Q000494:pharmacology*; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014945:Wound Healing; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D001786:Blood Glucose; D008565:Membrane Proteins; D051419:Paxillin; D034741:RNA, Small Interfering; C113267:nephrin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D054460:rho-Associated Kinases; D005947:Glucose