Dual function of TGFβ in lens epithelial cell fate: implications for secondary cataract
| Autor: | Judith A. West-Mays, Anna Korol, Bruce A. Boswell, Linda S. Musil |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
p38 mitogen-activated protein kinases Cell Chick Embryo Epithelium 03 medical and health sciences 0302 clinical medicine Cell Movement Transforming Growth Factor beta Lens Crystalline medicine Animals Humans Eye Proteins Myofibroblasts Molecular Biology Cell Proliferation biology Cell Differentiation Epithelial Cells Cell migration Articles Cell Biology eye diseases Lens Fiber Cell biology 030104 developmental biology medicine.anatomical_structure Fiber cell Cell Biology of Disease Mitogen-activated protein kinase Lens (anatomy) cardiovascular system 030221 ophthalmology & optometry biology.protein human activities Myofibroblast circulatory and respiratory physiology Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | TGFβ signaling is linked to posterior capsule opacification (PCO), the most common complication of cataract surgery. TGFβ can induce primary lens epithelial cells to differentiate into two disparate, PCO-causing abnormal cell phenotypes, a variation of the TGFβ paradox. Analysis of the signaling pathways downstream of TGFβ reveals novel therapeutic targets for PCO. The most common vision-disrupting complication of cataract surgery is posterior capsule opacification (PCO; secondary cataract). PCO is caused by residual lens cells undergoing one of two very different cell fates: either transdifferentiating into myofibroblasts or maturing into lens fiber cells. Although TGFβ has been strongly implicated in lens cell fibrosis, the factors responsible for the latter process have not been identified. We show here for the first time that TGFβ can induce purified primary lens epithelial cells within the same culture to undergo differentiation into either lens fiber cells or myofibroblasts. Marker analysis confirmed that the two cell phenotypes were mutually exclusive. Blocking the p38 kinase pathway, either with direct inhibitors of the p38 MAP kinase or a small-molecule therapeutic that also inhibits the activation of p38, prevented TGFβ from inducing epithelial–myofibroblast transition and cell migration but did not prevent fiber cell differentiation. Rapamycin had the converse effect, linking MTOR signaling to induction of fiber cell differentiation by TGFβ. In addition to providing novel potential therapeutic strategies for PCO, our findings extend the so-called TGFβ paradox, in which TGFβ can induce two disparate cell fates, to a new epithelial disease state. |
| Databáze: | OpenAIRE |
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