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 Aβ aggregates, 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 (MAP-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 A β-(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 Aβ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 219-228 |
| Number of pages | 10 |
| Journal | Yonsei Medical Journal |
| Volume | 45 |
| Issue number | 2 |
| Publication status | Published - 2004 Apr 30 |
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Keywords
- Amyloid
- Cataractogenesis
- Epithelial cells
- Extra-cellular matrix
- Growth factors
- Lens differentiation
ASJC Scopus subject areas
- Medicine(all)
Cite this
Possible role of amyloid β-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells. / Lee, Kwang Won; Seomun, Young; Kim, Dong Hwan; Park, Sun Young; Joo, Choun K.
In: Yonsei Medical Journal, Vol. 45, No. 2, 30.04.2004, p. 219-228.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Possible role of amyloid β-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells
AU - Lee, Kwang Won
AU - Seomun, Young
AU - Kim, Dong Hwan
AU - Park, Sun Young
AU - Joo, Choun K.
PY - 2004/4/30
Y1 - 2004/4/30
N2 - 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 Aβ aggregates, 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 (MAP-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 A β-(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 Aβ 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.
AB - 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 Aβ aggregates, 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 (MAP-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 A β-(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 Aβ 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.
KW - Amyloid
KW - Cataractogenesis
KW - Epithelial cells
KW - Extra-cellular matrix
KW - Growth factors
KW - Lens differentiation
UR - http://www.scopus.com/inward/record.url?scp=2442708887&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442708887&partnerID=8YFLogxK
M3 - Article
VL - 45
SP - 219
EP - 228
JO - Yonsei Medical Journal
JF - Yonsei Medical Journal
SN - 0513-5796
IS - 2
ER -