Effect of advanced glycation end products on lens epithelial cells in vitro.
The extended exposure of proteins to reducing sugars leads to nonenzymatic glycation with the accumulation of advanced glycation end products (AGEs). Long-lived proteins, such as collagen and crystallins, are subjected to this modification, and are implicated as causal factors in several diseases including diabetic complications, cataracts, and arteriosclerosis. One means through which AGEs modulate cellular interactions is via binding to specific receptors. In the current study, the existence of AGEs in human anterior polar lens capsules of cataracts was confirmed using a combination of dot-immunoblot and fluorescent detection. Human lens epithelial cells (LECs) attached to anterior lens capsules expressed mRNA for the receptor for AGEs (RAGE). The interaction of LECs with AGEs using bovine lens epithelial explants demonstrated that AGEs induced mRNAs and proteins of fibronectin, collagen type I, aberrant extracellular matrix proteins, and alpha-SMA, a specific marker for myofibroblastic cells. These findings suggest that AGEs may alter cellular functions which induce mRNAs and proteins associated with fibrosis in LECs.
Hong
S B
SB
Department of Ophthalmology and Visual Science, Catholic University of Korea, Seoul, Korea.
Lee
K W
KW
Handa
J T
JT
Joo
C K
CK
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002457:Cell Extracts; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007903:Lens Capsule, Crystalline / Q000378:metabolism* / Q000473:pathology; D009130:Muscle, Smooth / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D015854:Up-Regulation
D000199:Actins; D002457:Cell Extracts; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003094:Collagen