Leptin and connective tissue growth factor in advanced glycation end-product-induced effects in NRK-49F cells

✍ Scribed by Chu-I Lee; Jinn-Yuh Guh; Hung-Chun Chen; Kuan-Hua Lin; Yu-Lin Yang; Wen-Chun Hung; Yung-Hsiung Lai; Lea-Yea Chuang

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 369 KB
• Volume: 93
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20222

✦ Synopsis

Abstract

Previously, we showed that Janus kinase 2 (JAK2) is important in advanced glycation end‐product (AGE)‐induced effects in renal interstitial (NRK‐49F) fibroblasts. Leptin is a JAK2‐activating cytokine via the long form leptin receptor (Ob‐Rb). Leptin and connective tissue growth factor (CTGF) may be involved in renal fibrosis. However, the relationship between leptin and CTGF in terms of AGE‐induced effects remains unknown. Thus, the effects of AGE (150 μg/ml) and leptin on mitogenesis, CTGF and collagen expression in NRK‐49F cells were determined. We found that leptin and AGE increased mitogenesis and type I collagen protein expression at 3 and 7 days, respectively. AGE increased leptin mRNA and protein expression at 2–3 days. AGE increased CTGF mRNA and protein expression at 3–5 days. AG‐490 (JAK2 inhibitor) abrogated AGE‐induced leptin mRNA and protein expression at 2–3 days. AG‐490 and Ob‐Rb anti‐sense oligodeoxynucleotides (ODN) abrogated AGE‐induced CTGF mRNA and protein expression at 3–5 days. AG‐490 and CTGF anti‐sense ODN abrogated AGE‐induced mitogenesis and collagen protein expression at 7 days. Additionally, leptin dose (0.2–1 μg/ml) and time (1–2 days)‐dependently increased CTGF protein expression. AG‐490 abrogated leptin (1 μg/ml)‐induced CTGF protein expression at 2 days. AG‐490 and CTGF anti‐sense ODN abrogated leptin‐induced mitogenesis and collagen protein expression at 3 days. We concluded that AGE induced JAK2 to increase leptin while leptin induced JAK2 to increase CTGF‐induced mitogenesis and type I collagen protein expression in NRK‐49F cells. Additionally, AGE‐induced mitogenesis and type I collagen protein expression were dependent on leptin‐induced CTGF. © 2004 Wiley‐Liss, Inc.