Advanced glycation end-product-induced mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cells.
Diabetic nephropathy (DN) is characterized by glomerulopathy and tubulointerstitial expansion followed by renal fibrosis. Angiotensin II (Ang II) and connective tissue growth factor (CTGF) are involved in the pathogenesis of DN, while Janus kinase 2 (JAK2) is important in advanced glycation end-product (AGE)-induced effects in renal interstitial (NRK-49F) fibroblasts. Thus, we studied the role of Ang II, CTGF, and JAK2 in AGE-induced effects in NRK-49F cells. We found that AGE (150 microg/ml) increased mitogenesis and type I collagen production at 7 days while Ang II (10(-7)M) increased mitogenesis and type I collagen production at 3 days. We also found that AGE (150 microg/ml) increased angiotensinogen protein at 2 days, which was attenuated by AG-490 (a JAK2 inhibitor). AGE (150 microg/ml) increased CTGF mRNA and protein expression at 3 and 5 days, respectively. Ang II (10(-7)M) increased CTGF mRNA and protein expression at 1 and 2 days, respectively, which were attenuated by AG-490. Moreover, losartan (a type I angiotensin receptor blocker) and captopril (an angiotensin converting enzyme inhibitor) attenuated AGE-induced CTGF mRNA/protein expression while attenuating AGE-induced mitogenesis and type I collagen production. AG-490 and CTGF antisense (but not sense) oligodeoxynucleotide (ODN) attenuated Ang II (10(-7)M) and AGE-induced mitogenesis and type I collagen production at 3 and 7 days, respectively. We concluded that AGE (150 microg/ml)-induced mitogenesis and type I collagen production are dependent on the Ang II-JAK2-CTGF pathway in NRK-49F cells. Moreover, Ang II-induced mitogenesis and type I collagen production are dependent on the JAK2-CTGF pathway.
Lee
Chu-I
CI
Department of Medical Technology, Fooyin University, Kaohsiung, Taiwan.
Guh
Jinn-Yuh
JY
Chen
Hung-Chun
HC
Hung
Wen-Chun
WC
Yang
Yu-Lin
YL
Chuang
Lea-Yea
LY
D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D055513:Connective Tissue Growth Factor; D017931:DNA Primers; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D009841:Oligonucleotides / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D017931:DNA Primers; D017127:Glycation End Products, Advanced; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003094:Collagen