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 acetyl-transferase) 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 up-regulation of TβRII and fibronectin in hyperglycaemic distal-tubule cells.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
October 2003
- PDF Icon PDF LinkFront Matter
Research Article|
October 15 2003
Regulation of type II transforming-growth-factor-β receptors by protein kinase C ι
Lea-Yea CHUANG;
Lea-Yea CHUANG
∗Department of Biochemistry, Kaohsiung Medical University, Tainan, Taiwan
Search for other works by this author on:
Jinn-Yuh GUH;
Jinn-Yuh GUH
†Department of Internal Medicine, Kaohsiung Medical University, Tainan, Taiwan
Search for other works by this author on:
Shu-Fen LIU;
Shu-Fen LIU
†Department of Internal Medicine, Kaohsiung Medical University, Tainan, Taiwan
Search for other works by this author on:
Min-Yuan HUNG;
Min-Yuan HUNG
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Tung-Nan LIAO;
Tung-Nan LIAO
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
§Department of Medical Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Tai-An CHIANG;
Tai-An CHIANG
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
§Department of Medical Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Jau-Shyang HUANG;
Jau-Shyang HUANG
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
‖Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Yu-Lun HUANG;
Yu-Lun HUANG
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
‖Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Chi-Fong LIN;
Chi-Fong LIN
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
‖Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
Search for other works by this author on:
Yu-Lin YANG
Yu-Lin YANG
1
‡Institute of Biotechnology, Chung Hwa College of Medical Technology, Tainan, Taiwan
‖Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainan, Taiwan
1To whom correspondence should be addressed (e-mail [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 07 2003
Revision Received:
June 16 2003
Accepted:
July 04 2003
Accepted Manuscript online:
July 04 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 375 (2): 385–393.
Article history
Received:
April 07 2003
Revision Received:
June 16 2003
Accepted:
July 04 2003
Accepted Manuscript online:
July 04 2003
Citation
Lea-Yea CHUANG, Jinn-Yuh GUH, Shu-Fen LIU, Min-Yuan HUNG, Tung-Nan LIAO, Tai-An CHIANG, Jau-Shyang HUANG, Yu-Lun HUANG, Chi-Fong LIN, Yu-Lin YANG; Regulation of type II transforming-growth-factor-β receptors by protein kinase C ι. Biochem J 15 October 2003; 375 (2): 385–393. doi: https://doi.org/10.1042/bj20030522
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |