Fibroblast growth factor 2: roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury.
OBJECTIVE
To examine the role of fibroblast growth factor 2 (FGF2) in regulating 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 and transforming growth factor beta2 (TGFbeta2) on cell proliferation of alphaTN4 cells (a mouse lens epithelial cell line) were determined. FGF2-knockout mice were used to further examine the role of endogenous FGF2 on injury-induced epithelial cell proliferation and EMT. The anterior lens capsule was injured by a hypodermic needle under both general and topical anesthesia in one eye of 34 fgf2+/+ mice and 42 fgf2-/- mice. At days 2, 5, and 10 post-injury the mice were sacrificed following a 2 h labeling period with bromo-deoxyuridine (BrdU). The number of BrdU-positive cells in each specimen was determined.


RESULTS
A capsular break caused a 10 fold increase of FGF2 protein accumulated in rat lens 14 days after injury. Addition of 3.43 ng/ml FGF2 enhanced proliferation of alphaTN4 cells. This occurred in the presence or absence of exogenous TGFbeta2, that has an inhibitory effect on alphaTN4 cell proliferation. Significantly fewer BrdU-labeled cells were found in fgf2-/- mice than in fgf2+/+ mice during healing post-injury. However, lacking FGF2 did not alter the expression patterns of alpha-smooth muscle actin and collagen type I, markers of EMT in lens cells.


CONCLUSIONS
Endogenous FGF2 is required for increased cell proliferation but not essential for EMT during the lens response to injury.
Tanaka
Takeshi
T
Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. ttakeshi@land.linkclub.or.jp
Saika
Shizuya
S
Ohnishi
Yoshitaka
Y
Ooshima
Akira
A
McAvoy
John W
JW
Liu
Chia-Yang
CY
Azhar
Muhamad
M
Doetschman
Tomas
T
Kao
Winston Whei-Yang
WW
D000199:Actins / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002461:Cell Line, Transformed; D024042:Collagen Type I / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D015807:Eye Injuries, Penetrating / Q000378:metabolism / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007903:Lens Capsule, Crystalline / Q000293:injuries; D007908:Lens, Crystalline / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053781:Transforming Growth Factor beta2; D014945:Wound Healing
D000199:Actins; D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D016222:Fibroblast Growth Factor 2; D004247:DNA; D001973:Bromodeoxyuridine