Screening of potential target genes for cataract by analyzing mRNA expression profile of mouse Hsf4-null lens
نویسندگان
چکیده
BACKGROUND Hsf4 is closely related to the development of cataract. However, the molecular mechanisms remain unknown. This study aimed to explore the molecular mechanisms that how Hsf4 mutations influence development of lens and thus lead to cataract in mouse. METHODS The mRNA expression profile of mouse tissue samples from Hsf4-null and wile-type lenses was downloaded from Gene Expression Omnibus database. Then the LIMMA package was used to screen differentially expressed genes (DEGs) and DAVID was applied to identify the significantly enriched Gene Ontology (GO) categories for DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape and the key modules were selected from the PPI network based on the MCODE analysis. RESULTS A total of 216 DEGs were screened, including 51 up- and 165 down-regulated genes. Meanwhile, nine GO terms were obtained, and DEGs such as SGK1, CRY2 and REV1 were enriched in response to DNA damage stimulus. Furthermore, 89 DEGs and 99 gene pairs were mapped into the PPI network and Ubc was the hob node. Two key modules, which contained the genes (e.g. Ubc, Egr1, Ptgs2, Hmox1, Cd44, Btg2, Cyr61 and Fos) were related to response to DNA damage stimulus. CONCLUSIONS The deletion of Hsf4 affects the expression of many genes, such as Ubc, Ptgs2, Egr1 and Fos. These genes may be involved in the development of cataract and could be used as therapeutic targets for cataract.
منابع مشابه
HSF4 is required for normal cell growth and differentiation during mouse lens development.
The heat shock transcription factor (HSF) family consists of three members in mammals and regulates expression of heat shock genes via a heat shock element. HSF1 and HSF2 are required for some developmental processes, but it is unclear how they regulate these processes. To elucidate the mechanisms of developmental regulation by HSFs, we generated mice in which the HSF4 gene is mutated. HSF4-nul...
متن کاملIdentification of vimentin as a novel target of HSF4 in lens development and cataract by proteomic analysis.
PURPOSE To explore the target genes of HSF4, especially those involved in lens developmental processes and cataract formation. METHODS A slit lamp biomicroscopy examination was performed on Hsf4(tm1Xyk)-knockout mice and wild-type mice. Two-dimensional electrophoresis combined with mass spectrometry was used to identify differentially expressed lens proteins between wild-type and Hsf4(tm1Xyk)...
متن کاملMutation screening of HSF4 in 150 age-related cataract patients
PURPOSE Heat shock transcription factor 4 (HSF4) regulates the expression of several heat shock protein (HSP) genes. HSPs are one of the major components responsible for lens protein organization. Recently, we found that mutations of HSF4 result in hereditary cataract. In this study, we explore the role of HSF4 in the development of age-related cataract. METHODS We screened sequence variants ...
متن کاملExpression profile of developmentally important genes in pre- and peri-implantation goat embryos produced in vitro
Background Little is understood about the regulation of gene expression during early goat embryo development. This study investigated the expression profile of 19 genes, known to be critical for early embryo development in mouse and human, at five different stages of goat in vitro embryo development (oocyte, 8-16 cell, morula, day-7 blastocyst, and day 14 blastocyst). MaterialsAndMethods Stage-...
متن کاملA homozygous splice mutation in the HSF4 gene is associated with an autosomal recessive congenital cataract.
PURPOSE To map the locus and identify the gene causing autosomal recessive congenital cataracts in a large consanguineous Tunisian family. METHODS DNA was extracted from blood samples from a large Tunisian family with an autosomal recessive, congenital, total white cataract. A genome-wide scan was performed with microsatellite markers. All exons and the splice sites of the HSF4 gene were sequ...
متن کامل