Fibroblast growth factor 2: roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury.
Fibroblast growth factor 2: roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury.
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DOI：
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发表时间：
2004-07
期刊：
影响因子：
2.2
通讯作者：
Takeshi Tanaka;S. Saika;Y. Ohnishi;A. Ooshima;J. Mcavoy;Chia-Yang Liu;Muhamad Azhar;T. Doetschman;W. Kao
中科院分区：
文献类型：
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作者：
Takeshi Tanaka;S. Saika;Y. Ohnishi;A. Ooshima;J. Mcavoy;Chia-Yang Liu;Muhamad Azhar;T. Doetschman;W. Kao
目的探讨成纤维细胞生长因子2（FGF 2）在透镜细胞增殖和上皮间质转化（EMT）中的作用。方法采用酶免疫分析法测定大鼠晶状体损伤后愈合过程中FGF 2蛋白的含量。测定FGF 2和转化生长因子β 2（TGF β 2）对α TN 4细胞（小鼠透镜上皮细胞系）的细胞增殖的影响。使用FGF 2敲除小鼠进一步检查内源性FGF 2对损伤诱导的上皮细胞增殖和EMT的作用。在全身麻醉和表面麻醉下，在34只fgf 2 +/+小鼠和42只fgf 2-/-小鼠的一只眼睛中通过皮下注射针损伤前透镜囊。在损伤后第2、5和10天，用溴脱氧尿苷（BrdU）标记2小时后处死小鼠。测定每份标本中BrdU阳性细胞的数量。结果晶状体囊膜破裂后14 d，大鼠透镜内FGF 2蛋白的表达增加10倍。加入3.43 ng/ml FGF 2可增强alphaTN 4细胞的增殖。这发生在存在或不存在外源性TGF β 2的情况下，其对α TN 4细胞增殖具有抑制作用。在损伤后愈合期间，在fgf 2-/-小鼠中发现的BrdU标记的细胞显著少于fgf 2 +/+小鼠。然而，缺乏FGF 2并没有改变α-平滑肌肌动蛋白和I型胶原蛋白的表达模式，它们是透镜细胞中EMT的标志物。结论：在透镜对损伤的反应中，内源性FGF 2是增加细胞增殖所必需的，但不是EMT所必需的。
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 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.