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Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells

  1. Jau-Shyang Huang1,
  2. Jinn-Yuh Guh2,
  3. Hung-Chun Chen2,
  4. Wen-Chun Hung3,
  5. Yung-Hsiung Lai2,
  6. Lea-Yea Chuang1,*

Article first published online: 6 FEB 2001

DOI: 10.1002/1097-4644(20010401)81:1<102::AID-JCB1027>3.0.CO;2-Y

Issue

Journal of Cellular Biochemistry

Journal of Cellular Biochemistry

Volume 81, Issue 1, pages 102–113, 1 April 2001

Additional Information

How to Cite

Huang, J.-S., Guh, J.-Y., Chen, H.-C., Hung, W.-C., Lai, Y.-H. and Chuang, L.-Y. (2001), Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells. Journal of Cellular Biochemistry, 81: 102–113. doi: 10.1002/1097-4644(20010401)81:1<102::AID-JCB1027>3.0.CO;2-Y

Author Information

  1. 1

    Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

  2. 2

    Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

  3. 3

    School of Technology for Medical Science, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

*Department of Biochemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, Republic of China.

Publication History

  1. Issue published online: 6 FEB 2001
  2. Article first published online: 6 FEB 2001
  3. Manuscript Accepted: 13 SEP 2000
  4. Manuscript Received: 6 JUL 2000

Funded by

  • National Science Council, Republic of China. Grant Numbers: NSC-88-2316-B037-004, NSC-88-2314-B037-055.

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Keywords:

  • diabetic nephropathy;
  • advanced glycation end-product;
  • oligodeoxynucleotide;
  • tyrosine phosphorylation;
  • captopril

Abstract

Advanced glycation end-product (AGE) is important in the pathogenesis of diabetic nephropathy (DN), and captopril (an angiotensin converting enzyme inhibitor) is effective in treating this disorder. We have shown that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade is responsible for AGE-induced mitogenesis in NRK-49F (normal rat kidney fibroblast) cells, but its role in renal fibrosis in DN remains unknown. Therefore, we have sought to determine whether JAK/STAT is involved in AGE-regulated collagen production in NRK-49F cells. We found that AGE time (1–7 days) and dose (10–200 μg/ml)-dependently increased collagen production in these cells. Additionally, AGE increased RAGE (receptor for AGE) protein expression. AGE-induced RAGE expression was dose-dependently inhibited by antisense RAGE oligodeoxynucleotide (ODN) and captopril. AGE-induced type I collagen production and JAK2-STAT1/STAT3 activation were decreased by AG-490 (a specific JAK2 inhibitor), antisense RAGE ODN and captopril. Meanwhile, STAT1 and STAT3 decoy ODNs also suppressed the induction of collagen by AGE. We concluded that RAGE and the JAK2-STAT1/STAT3 pathway were involved in AGE-induced collagen production in NRK-49F cells. Furthermore, captopril was found to reverse AGE-induced collagen production, probably by attenuating RAGE expression and JAK2-STAT1/STAT3 activities. J. Cell. Biochem. 81:102–113, 2001. © 2001 Wiley-Liss, Inc.

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