Advanced glycation end-product-inhibited cell proliferation and protein expression of beta-catenin and cyclin D1 are dependent on glycogen synthase kinase 3beta in LLC-PK1 cells.
Glycogen synthase kinase 3beta (GSK3beta) is increased by high glucose in mesangial cells. Thus, we studied the role of GSK3beta in advanced glycation end-product (AGE)-induced effects in the proximal tubule-like LLC-PK1 cells. We found that AGE (100 microg/ml) time-dependently (8-48 h) increased phospho-GSK3beta-Tyr216 (active GSK3beta) and time-dependently (4-24 h) decreased phospho-GSK3beta-Ser21/9 (inactive GSK3beta) protein expression. Meanwhile, AGE (100 microg/ml) activated GSK3beta kinase at 8-48 h. AGE (100 microg/ml) dose-dependently (75-100 microg/ml) decreased beta-catenin protein expression but AGE did not decrease beta-catenin protein expression until 48 h. SB216763 (a GSK3beta inhibitor) and GSK3beta shRNA attenuated AGE (100 microg/ml)-inhibited cell proliferation and protein expression of beta-catenin and cyclin D1 at 48 h. SB216763 also attenuated AGE-induced type IV collagen. We conclude that AGE activates GSK3beta in LLC-PK1 cells. AGE-inhibited beta-catenin and cyclin D1 protein expression are dependent on GSK3beta. Moreover, AGE-inhibited cell proliferation and AGE-induced type IV collagen protein expression are dependent on GSK3beta.
Lin
Kuan-Hua
KH
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Guh
Jinn-Yuh
JY
Mo
Jen-Fong
JF
Chiou
Shean-Jaw
SJ
Hwang
Chi-Ching
CC
Chuang
Lea-Yea
LY
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D047468:Immunoprecipitation; D007211:Indoles / Q000494:pharmacology; D018374:LLC-PK1 Cells; D008301:Maleimides / Q000494:pharmacology; D013552:Swine; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D051176:beta Catenin; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3