Possible role of amyloid beta-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells.
We investigated whether amyloid beta(Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferentiation of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta-(1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta-(1-40)-BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta-(1-40)-BSA, and the immunohistochemical localizations of Abeta-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta-(1-40)-BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.
Lee
Kwang-Won
KW
Division of Food Science, College of Life and Environmental Sciences, Korea University, Seoul, Korea.
Seomun
Young
Y
Kim
Dong-Hwan
DH
Park
Sun-Young
SY
Joo
Choun-Ki
CK
D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics*; D000818:Animals; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012710:Serum Albumin, Bovine