Journal
EXPERIMENTAL CELL RESEARCH
Volume 293, Issue 1, Pages 175-183Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexcr.2003.09.022
Keywords
thymosin beta 4; cornea; epithelial cell; cell migration; laminin-5; TGF-beta; cytokines; extracellular matrix
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Funding
- NEI NIH HHS [K08 EY13412] Funding Source: Medline
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Thymosin beta 4 (Tbeta(4)) stimulates epithelial cell migration and promotes laminin-5 (LM-5) expression. Using gene expression analysis with human corneal epithelial cells treated with Tbeta(4), we find that both LM-5 gamma2 chain and transforming growth factor beta 1 (TGFbeta-1) are increased by more than 2-fold over untreated cells. These findings were confirmed by RT-PCR and at the protein level. Although TGFbeta-1 increases LM-5 synthesis in a dose-dependent manner, it does not appear to be the mechanism by which Tbeta(4) acts on LM-5 gamma2 chain synthesis based on three independent experiments. In a time-course analysis, Tbeta(4) increases LM-5 gamma2 chain expression at 2 h and peaks at 6 h, while TGFbeta-1 increases LM-5 gamma2 chain expression only at 4 h and peaks at 8 h. When Tbeta(4)-induced LM-5 gamma2 chain expression is blocked with neutralizing antibodies to TGFbeta-1, LM-5 gamma2 chain expression is increased. Finally, in TGFbeta-1 knock-out mice, Tbeta(4) increases LM-5 gamma2 chain expression to levels higher than that observed in wild-type mice treated with Tbeta(4). These findings demonstrate that Tbeta(4) induces both TGFbeta-1 and LM-5 gamma2 chain expression in corneal epithelial cells. Tbeta(4) and TGFbeta-1 increase LM-5 2 gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further increases LM-5 gamma2 chain expression. (C) 2003 Elsevier Inc. All rights reserved.
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