Leptin and connective tissue growth factor in advanced glycation end-product-induced effects in NRK-49F cells.
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 microg/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 microg/ml) and time (1-2 days)-dependently increased CTGF protein expression. AG-490 abrogated leptin (1 microg/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.
Lee
Chu-I
CI
Department of Medical Technology, Fooyin University, Kaohsiung, Taiwan.
Guh
Jinn-Yuh
JY
Chen
Hung-Chun
HC
Lin
Kuan-Hua
KH
Yang
Yu-Lin
YL
Hung
Wen-Chun
WC
Lai
Yung-Hsiung
YH
Chuang
Lea-Yea
LY
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2; D007684:Kidney Tubules / Q000166:cytology; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats
C526316:CCN2 protein, rat; D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D055513:Connective Tissue Growth Factor; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2