Identification of functional pathways associated with the conditional ablation of serum response factor in Dstncorn1 mice

Abstract

The aim of the present study was to investigate the signaling pathways associated with functional alterations in corneal tissues following the conditional ablation of serum response factor (Srf) in Dstncorn1 mice. The gene expression profiling array GSE49688, which includes 3 samples each from the wild-type (WT), Dstncorn1 mutant (corn1) and corn1 mice following the conditional ablation of Srf from the corneal epithelium [namely rescued (res)] mouse groups, was downloaded from the Gene Expression Omnibus database. The limma package was used to identify differentially expressed genes (DEGs) among the three mouse groups. DEGs were subsequently analyzed by dynamic comparison, hierarchical clustering and pathway enrichment analysis. Pathway alteration scores were also calculated in order to study the dynamic metergasis of each identified pathway. A total of 788 DEGs were identified between the corn1 and res groups, 1,365 DEGs were identified between the corn1 and WT groups, and 852 DEGs were identified between the res and WT groups. Among these DEGs, 228 genes were differentially expressed across all three groups, and were mainly enriched in signaling pathways involved in the regulation of the actin cytoskeleton, including the cofilin 1 (CFL1), the mitogen-activated protein kinase (MAPK) signaling pathway and focal adhesion. The dilated cardiomyopathy signaling pathway displayed the highest alteration score, and was enriched with integrin and integrin β-6 (ITGB6). In conclusion, the actin cytoskeleton regulatory pathway, MAPK and dilated cardiomyopathy signaling pathways, as well as CFL1 and ITGB6 genes, may be regulated by Srf to serve important roles in the progression of corneal disease.

The actin-binding protein CAP1 represses MRTF-SRF–dependent gene expression in mouse cerebral cortex

“…Although cofilin1 and ADF have been implicated in MRTF-SRF regulation in cardiomyocytes and corneas (53)(54)(55), we found neuronal SRF activity unchanged upon inactivation of cofilin1 or ADF. Instead, SRF activity was moderately increased in ADF/Cfl1-dKO neurons, in line with studies demonstrating overlapping brain functions for both ABPs (22)(23)(24)56).…”