Premium
Role of receptor for advanced glycation end‐product (RAGE) and the JAK/STAT‐signaling pathway in AGE‐induced collagen production in NRK‐49F cells
Author(s) -
Huang JauShyang,
Guh JinnYuh,
Chen HungChun,
Hung WenChun,
Lai YungHsiung,
Chuang LeaYea
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20010401)81:1<102::aid-jcb1027>3.0.co;2-y
Subject(s) - rage (emotion) , janus kinase , advanced glycation end product , stat3 , glycation , medicine , endocrinology , stat1 , signal transduction , jak stat signaling pathway , chemistry , janus kinase 2 , receptor , cancer research , biology , microbiology and biotechnology , tyrosine kinase , neuroscience
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.