title: High glucose induces sumoylation of Smad4 via SUMO2/3 in mesangial cells.
abstract: Recent studies have shown that sumoylation is a posttranslational modification involved in regulation of the transforming growth factor-β (TGF-β) signaling pathway, which plays a critical role in renal fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of TGF-β signaling in DN is still unclear. In the present study, we investigated the expression of SUMO (SUMO1 and SUMO2/3) and Smad4 and the interaction between SUMO and Smad4 in cultured rat mesangial cells induced by high glucose. We found that SUMO1 and SUMO2/3 expression was significantly increased in the high glucose groups compared to the normal group (P < 0.05). Smad4 and fibronectin (FN) levels were also increased in the high glucose groups in a dose-dependent manner. Coimmunoprecipitation and confocal laser scanning revealed that Smad4 interacted and colocalized with SUMO2/3, but not with SUMO1 in mesangial cells. Sumoylation (SUMO2/3) of Smad4 under high glucose condition was strongly enhanced compared to normal control (P < 0.05). These results suggest that high glucose may activate TGF- β/Smad signaling through sumoylation of Samd4 by SUMO2/3 in mesangial cells.
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China ; Department of Endocrinology, The Central Hospital of Bazhong City, Sichuan 636000, China.
authors: Xueqin
authors: X
authors: Zhou
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Chenlin
authors: 0000-0003-2464-9325
authors: C
authors: Gao
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Wei
authors: W
authors: Huang
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Maojun
authors: M
authors: Yang
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Guo
authors: G
authors: Chen
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Lan
authors: L
authors: Jiang
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Fang
authors: F
authors: Gou
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Hong
authors: H
authors: Feng
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Na
authors: N
authors: Ai
authors: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors: Yong
authors: 0000-0002-9534-6252
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D002460:Cell Line; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000187:drug effects*
chemical_list: D005353:Fibronectins; D012333:RNA, Messenger; C529669:SUMO2 protein, rat; C529670:SUMO3 protein, rat; D051901:Smad4 Protein; D025841:Small Ubiquitin-Related Modifier Proteins; D005947:Glucose