Galectin-1 influences migration of retinal pigment epithelial cells.
PURPOSE: To determine whether the beta-galactoside-binding matricellular protein Gal-1 is expressed in human specimens of proliferative vitreoretinopathy (PVR) and to evaluate its influence on RPE migration. METHODS: RT-PCR was used to detect Gal-1-specific transcripts in PVR membranes, and the expression pattern of Gal-1 was examined by immunohistochemistry. Expression of Gal-1 in native, low- and high-density cultured RPE cells was determined by Western blot analysis. Cultured human RPE cells were treated with bFGF, TGF-beta2, PDGF-BB, or HGF. The dose-response of Gal-1 mRNA expression was measured by by real-time quantitative RT-PCR and Northern blot analysis. Induction of Gal-1 protein was confirmed by Western blot analysis. To study the effect of Gal-1 on RPE migration in vitro, Gal-1 expression was silenced by RNA interference. beta-Lactose was used to saturate extracellular galectins. RPE cell migration was assessed by a modified Boyden chamber assay, with HGF as the chemoattractant. RESULTS: Gal-1 mRNA expression was present in human specimens of PVR membranes, and staining for Gal-1 was distributed throughout the extracellular matrix ( ECM) of PVR membranes. Colocalization was found with laminin and fibronectin and cells of epithelial origin. Western blot analysis revealed greater baseline expression levels in low-density cultured RPE cells than in native and high-density cultured RPE cells. Treatment with HGF caused a dose-dependent increase in Gal-1 expression. Low expression levels of Gal-1 correlated with a reduction of RPE migration to 14% of control. beta-Lactose inhibited HGF- induced RPE cell migration to 23% of control. CONCLUSIONS: Gal-1 is present in the extracellular matrix of PVR membranes and may be derived from dedifferentiated RPE cells. The expression level of Gal-1 appears to be related to a migratory RPE phenotype and stimulation by HGF, both conditions implicated in the pathogenesis of early PVR. Furthermore, HGF- induced RPE migration may be dependent, at least in part, on Gal-1- and beta-galactoside-dependent mechanisms.[1]References
- Galectin-1 influences migration of retinal pigment epithelial cells. Alge, C.S., Priglinger, S.G., Kook, D., Schmid, H., Haritoglou, C., Welge-Lussen, U., Kampik, A. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
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