Regulation of type II transforming-growth-factor-β receptors by protein kinase C ι

被引：0

作者：

Chuang, Lea-Yea ^{[1
]}

Guh, Jinn-Yuh ^{[2
]}

Liu, Shu-Fen ^{[2
]}

Hung, Min-Yuan ^{[3
]}

Liao, Tung-Nan ^{[3
,4
]}

Chiang, Tai-An ^{[3
,4
]}

Huang, Jau-Shyang ^{[3
,5
]}

Huang, Yu-Lun ^{[3
,5
]}

Lin, Chi-Fong ^{[3
,5
]}

Yang, Yu-Lin ^{[3
,5
]}

机构：

[1] Department of Biochemistry, Kaohsiung Medical University, Tainan

[2] Department of Internal Medicine, Kaohsiung Medical University, Tainan

[3] Institute of Biotechnology, Chung Hwa Coll. of Med. Technology, Tainan

[4] Department of Medical Technology, Chung Hwa Coll. of Med. Technology, Tainan

[5] Dept. of Biol. Sci. and Technology, Chung Hwa Coll. of Med. Technology, Tainan

来源：

Biochemical Journal | 2003年 / 375卷 / 02期

关键词：

Diabetic nephropathy; Glucose; Isoforms; Protein kinase C; Signal transduction; Transforming-growth-factor-β; receptor;

D O I：

10.1042/BJ20030522

中图分类号：

学科分类号：

摘要：

TGF-β (transforming growth factor-β) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-β receptor (TβRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. We have elucidated the mechanism by using cultured Madin-Darby canine kidney cells. Enhancer assay and electrophoretic-mobility-shift assay were used to estimate the involvement of transcription factors. Western blotting and an in vitro kinase assay were used to evaluate the level and activity of protein kinase. We showed that glucose (100-900 mg/ dl) induced an increase in mRNA level and promoter activity of TβRII (note: 'mg/dl' are the units commonly used in diabetes studies). The promoter region -209 to -177 appeared to contribute to positive transactivation of TβRII promoter by comparing five TβRII-promoter-CAT (chloramphenicol acetyltransferase) plasmids. Moreover, the transcription factor AP-1 (activator protein 1) was significantly activated and specifically binds to TβRII promoter ( -209 to -177). More importantly, we found that atypical PKC ι might be pivotal for high glucose-induced increase in both AP-1 binding and TβRII promoter activity. First, high glucose induced cytosolic translocation, activation and autophosphorylation of PKC ι. Secondly, antisense PKC ι expression plasmids attenuated high-glucose-induced increase in AP-1 binding and TβRII promoter activity; moreover, sense PKC ι expression plasmids enhanced these instead. Finally, we showed that antisense PKC ι expression plasmids might partly attenuate a high-glucose/TGF-β1-induced increase in fibronectin. We conclude that PKC ι might mediate high-glucose-induced increase in TβRII promoter activity. In addition, antisense PKC ι expression plasmid effectively suppressed upregulation of TβRII and fibronectin in hyperglycaemic distal-tubule cells.

引用

页码：385 / 393

页数：8

共 52 条

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