The Over-expression Of Lmx1b Inhibits TGF-β Signal Pathway In Rat Corneal Stromal Cells

Glaucoma is a major factor causing blindness, but there is no good treatment by now. Researchers are inclined to think that its etiology is mainly related to genetic factors. So finding out the pathogenic gene can provides a different approach to cure this disease.Lmxlb is a member of LIM homeobox transcription factor. It is involved in the development of different organs. It has reported that Lmxlb was expressed in mouse corneal endothelium, corneal stroma and trabecular meshwork. Mutation of Lmxlb can change the structure of anterior segments, much more worse, it can increase the intraocular pressure. These symptoms will cause glaucoma. Therefore, Lmxlb is closely related to glaucoma, but the mechanism is unclear in cornea. In this study, we constructed recombinant expression vector(pEGFP-Lmxlb) and over expressed it in rat corneal stromal cells. We obtained the corneal stromal cells transcriptome by RNA sequencing. We found 305 genes were differently expressed(treated vs control), in which 89 genes were significantly up-regulated and 216 genes were significantly down-regulated in response to Lmxlb over expression. KEGG was used to find out the canonical pathways associated with the differentially expressed genes. TGF-β signaling pathway, focal adhension, ECM-receptor interaction, regulation of actin cytoskeleton and cytokine-cytokine receptor interaction were major classes. Further more, Chordin, BMP, Smad8, Actin, Collagen, Vimentin, ELN and ITGA are implicated in these pathways. Take togenther, we hold that Lmxlb may regulate the cytoskeleton and collagen by TGF-β signal pathway.These signal pathways and genes not only shed new light on the understanding of pathogenesis mechanism of Lmxlb, but also establish the molecular basis for the treatment of glaucoma.