Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta

• Published in: Experimental cell research 2004-02, Vol.293 (1), p.175-183
• Main Authors: Sosne, Gabriel, Xu, Lihua, Prach, Lisa, Mrock, Linda K, Kleinman, Hynda K, Letterio, John J, Hazlett, Linda D, Kurpakus-Wheater, Michelle
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line; Cornea - cytology; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation - drug effects; Humans; Kalinin; Kinetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Thymosin - pharmacology; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology
• ISSN: 0014-4827
• DOI: 10.1016/j.yexcr.2003.09.022

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 gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further increases LM-5 gamma2 chain expression.