Fibroblast growth factor 2: Roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury

Takeshi Tanaka, Shizuya Saika, Yoshitaka Ohnishi, Akira Ooshima, John W. McAvoy, Chia Yang Liu, Muhamad Azhar, Thomas C Doetschman, Winston Whei Yang Kao

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: 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 β2 (TGFβ2) on cell proliferation of αTN4 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 αTN4 cells. This occurred in the presence or absence of exogenous TGFβ2, that has an inhibitory effect on αTN4 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 α-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.

Original languageEnglish (US)
Pages (from-to)462-467
Number of pages6
JournalMolecular Vision
Volume10
StatePublished - Jul 15 2004
Externally publishedYes

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Epithelial-Mesenchymal Transition
Fibroblast Growth Factor 2
Lenses
Cell Proliferation
Wounds and Injuries
Deoxyuridine
Transforming Growth Factors
Anterior Capsule of the Lens
Epithelial Cells
Collagen Type I
Immunoenzyme Techniques
Knockout Mice
General Anesthesia
Needles
Smooth Muscle
Actins
Proteins
Cell Line

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Tanaka, T., Saika, S., Ohnishi, Y., Ooshima, A., McAvoy, J. W., Liu, C. Y., ... Kao, W. W. Y. (2004). Fibroblast growth factor 2: Roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury. Molecular Vision, 10, 462-467.

Fibroblast growth factor 2 : Roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury. / Tanaka, Takeshi; Saika, Shizuya; Ohnishi, Yoshitaka; Ooshima, Akira; McAvoy, John W.; Liu, Chia Yang; Azhar, Muhamad; Doetschman, Thomas C; Kao, Winston Whei Yang.

In: Molecular Vision, Vol. 10, 15.07.2004, p. 462-467.

Research output: Contribution to journalArticle

Tanaka, T, Saika, S, Ohnishi, Y, Ooshima, A, McAvoy, JW, Liu, CY, Azhar, M, Doetschman, TC & Kao, WWY 2004, 'Fibroblast growth factor 2: Roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury', Molecular Vision, vol. 10, pp. 462-467.
Tanaka, Takeshi ; Saika, Shizuya ; Ohnishi, Yoshitaka ; Ooshima, Akira ; McAvoy, John W. ; Liu, Chia Yang ; Azhar, Muhamad ; Doetschman, Thomas C ; Kao, Winston Whei Yang. / Fibroblast growth factor 2 : Roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury. In: Molecular Vision. 2004 ; Vol. 10. pp. 462-467.
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abstract = "Purpose: 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 β2 (TGFβ2) on cell proliferation of αTN4 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 αTN4 cells. This occurred in the presence or absence of exogenous TGFβ2, that has an inhibitory effect on αTN4 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 α-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.",
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AU - Ooshima, Akira

AU - McAvoy, John W.

AU - Liu, Chia Yang

AU - Azhar, Muhamad

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