Human VEGFC peptide

Here we intended to depict the dynamic changes of gene expression profiles during the recovery phase of severed rat medial collateral ligament (MCL). The GSE10720 gene expression profiles of severed rat MCL after 1, 2, 4, 7, 10 and 14 day(s) of injury were downloaded from Gene Expression Omnibus (GEO) database. STEM (Short Time-series Expression Miner) software was conducted to cluster genes with similar expression patterns, followed by identification of differentially expressed genes (DEGs) between injured group and sham control group, Gene Ontology (GO) annotation and pathway enrichment analysis. Subsequently, gene functional interaction (FI) network and protein-protein interaction (PPI) network were respectively constructed using Reactome FI and STRING. Transcription factors (TFs) were predicted by Animal TFDB. Three significant temporal expression patterns were uncovered after MCL injury, among which the most significant cluster consisted of 3854 DEGs. Of these DEGs, 102 constructed the gene FI network consisting of 9 significant modules. GO analysis revealed that cell differentiation was the most significant GO term enriched by 240 DEGs, and among these DEGs, 33 genes, such as EGFR, VEGFC, ITGAV, ITGA1, significantly enriched in both focal adhesion and ECM-receptor interaction pathways. PPI network demonstrated 10 genes with degree > 20. Totally 22 TFs were predicted to target to these 240 DEGs. The expression profiles of severed rat MCL significantly changed during the recovery phase. DEGs in the early 14 days of MCL healing, such as VEGFC, EGFR, ITGAV and LAMB2, are more likely to play essential roles during this process.

Previous studies showed that transcripts encoding specific Wnt ligands and Frizzled receptors including Wnt4, Frizzled1 (Fzd1), and Frizzled4 (Fzd4) were expressed in a cell-specific manner in the adult mouse ovary. Overlapping expression of Wnt4 and Fzd4 mRNA in small follicles and corpora lutea led us to hypothesize that the infertility of mice null for Fzd4 (Fzd4(-/-)) might involve impaired follicular growth or corpus luteum formation. Analyses at defined stages of reproductive function indicate that immature Fzd4(-/-) mouse ovaries contain follicles at many stages of development and respond to exogenous hormone treatments in a manner similar to their wild-type littermates, indicating that the processes controlling follicular development and follicular cell responses to gonadotropins are intact. Adult Fzd4(-/-) mice also exhibit normal mating behavior and ovulate, indicating that endocrine events controlling these processes occur. However, Fzd4(-/-) mice fail to become pregnant and do not produce offspring. Histological and functional analyses of ovaries from timed mating pairs at Days 1.3-7.5 postcoitus (p.c.) indicate that the corpora lutea of the Fzd4(-/-) mice do not-develop normally. Expression of luteal cell-specific mRNAs (Lhcgr, Prlr, Cyp11a1 and Sfrp4) is reduced, luteal cell morphology is altered, and markers of angiogenesis and vascular formation (Efnb1, Efnb2, Ephb4, Vegfa, Vegfc) are low in the Fzd4(-/-) mice. Although a recently identified, high-affinity FZD4 ligand Norrin (Norrie disease pseudoglioma homolog) is expressed in the ovary, adult Ndph(-/-) mice contain functional corpora lutea and do not phenocopy Fzd4(-/-) mice. Thus, Fzd4 appears to impact the formation of the corpus luteum by mechanisms that more closely phenocopy Prlr null mice.