Advanced glycation end products inhibit tubulogenesis and migration of kidney epithelial cells in an ezrin-dependent manner.
Nonenzymatic glycation of proteins to form advanced glycation end products (AGE) is implicated in diabetic complications, including nephropathy. It was shown recently that AGE bind to the ERM (ezrin, radixin, and moesin) family of membrane-cytoskeletal linker proteins in renal homogenates. Herein is reported the effects of AGE-BSA on ezrin-dependent LLC-PK1 kidney epithelial cellular functions: migration and hepatocyte growth factor (HGF)-induced tubulogenesis. LLC-PK1 cells were stably transfected with cDNA for ezrin sense, ezrin antisense, and N-ezrin. Transfection of LLC-PK1 cells with ezrin antisense and dominant negative N-ezrin decreased basal tubulogenesis and migration relative to vector-only transfection, establishing the ezrin dependency of these processes. AGE-BSA (20 or 40 microM) significantly decreased HGF-induced tubulogenesis and basal migration in two vector control lines relative to BSA-treated cells. However, AGE-BSA inhibition of both HGF-induced tubulogenesis and migration was overcome by overexpressing ezrin. These results demonstrate that the AGE-ezrin interaction significantly alters cellular function. These changes may be relevant to detrimental renal consequences as a result of diabetes.
Gallicchio
Marisa A
MA
Monash University, Department of Medicine, Alfred Hospital, Commercial Road, Prahran, Victoria 3004, Australia.
McRobert
E Anne
EA
Tikoo
Anjali
A
Cooper
Mark E
ME
Bach
Leon A
LA
D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018374:LLC-PK1 Cells; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013552:Swine; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D017127:Glycation End Products, Advanced; D017228:Hepatocyte Growth Factor; D012710:Serum Albumin, Bovine; D000099149:Ezrin; C081628:advanced glycation end products-bovine serum albumin