Fibroblast growth factor 2: Roles of regulation of lens cellproliferation and epithelial-mesenchymal transition in response toinjury

[摘要] Purpose: To examine the role of fibroblast growth factor 2 (FGF2) inregulating lens cell proliferation and epithelial-mesenchymal transition(EMT) in response to injury.Methods: The amount of FGF2 protein was determined in healing,injured rat lenses by enzyme immunoassay. The effects of FGF2 andtransforming growth factor β2 (TGFβ2) on cell proliferation ofαTN4 cells (a mouse lens epithelial cell line) were determined.FGF2-knockout mice were used to further examine the role of endogenousFGF2 on injury-induced epithelial cell proliferation and EMT. Theanterior lens capsule was injured by a hypodermic needle under bothgeneral and topical anesthesia in one eye of 34 fgf2+/+ miceand 42 fgf2-/- mice. At days 2, 5, and 10 post-injury the micewere sacrificed following a 2 h labeling period with bromo-deoxyuridine(BrdU). The number of BrdU-positive cells in each specimen wasdetermined.Results: A capsular break caused a 10 fold increase of FGF2 proteinaccumulated in rat lens 14 days after injury. Addition of 3.43 ng/mlFGF2 enhanced proliferation of αTN4 cells. This occurred in thepresence or absence of exogenous TGFβ2, that has an inhibitoryeffect on αTN4 cell proliferation. Significantly fewerBrdU-labeled cells were found in fgf2-/- mice than infgf2+/+ mice during healing post-injury. However, lacking FGF2did not alter the expression patterns of α-smooth muscle actin andcollagen type I, markers of EMT in lens cells.Conclusions: Endogenous FGF2 is required for increased cellproliferation but not essential for EMT during the lens response toinjury.

[学科分类] 生物化学/生物物理