Possible Role of Amyloid B-(1-40)-BSA Conjugates in Transdifferentiation of Lens Epithelial Cells|RISS 상세보기

다국어 초록 (Multilingual Abstract)

We investigated whether amyloid β (Aβ) aggregates have transforming growth factor β- like cytokine activity and cause transdifferention of lens epithelial cells, leading to certain types of cataract. In order to mimic Aβaggregates, Aβ-(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 Aβ-(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 Aβ-(1-40)-BSA, and the immunohistochemical localizations of Aβ-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Aβ-(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 Aβ/APP in human clinical tissues revealed that the predominant immunostaining of Aβ occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Aβaggregates 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.

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