As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are invol...As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are involved in innate immunity.Japanese flounder is an economically important marine flatfish.In this study,two homologous genes of MUC2 were identified,named MUC2-1 and MUC2-2.Depending on phylogenetic and structural analysis,MUC2-1 and MUC2-2 were clustered in two clades,respectively.Paralichthys olivaceus MUC2-1 showed a closer relationship with MUC2 in the higher vertebrates.Various healthy tissues were analyzed to determine the expression patterns,and both MUC2 genes showed high expression levels in the gills and intestines.Following Edwardsiella tarda challenge,P.olivaceus MUC2-1 and MUC2-2 both showed significant up-regulated expression in intestine and kidney.Moreover,MUC2-1 was significantly up-regulated in gill cell lines following PGN and polyI:C stimulation,and MUC2-2 was significantly up-regulated in gill cell lines following LPS stimulation.In addition,ISH results revealed that MUC2-1 and MUC2-2 showed the same tissue localization in intestine tissues,but displayed different localization in gill.The siRNA-mediated knockdown of MUC2-1 and MUC2-2 genes in the gill cell lines of Japanese flounder affected the expressions of galnt family genes and smad pathway members that are related to mucosal immunity.The results provided a valuable insight into understanding the functions of MUC2 on mucosal immune system in response to the invasion of bacterial pathogen.展开更多
Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorect...Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorectal carcinoma remains unclear. Methods: We downloaded the GSE110223, GSE110224, GSE113513 and GSE122183 microarray datasets from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) related to F. nucleatum in CRC by overlapping data sets was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome pathway (KEGG) analyses were used for enrichment analysis. Moreover, Cytoscape software constructed a protein-protein interaction (PPI) network of differentially expressed genes. Finally, western blot and RT-qPCR analysis identified the relative protein and mRNA expression of hub genes in the cell model. Results: In total, 118 DEGs in F. nucleatum-associated CRC were screened from nonoverlapping microarray data, among which 20 upregulated and 98 downregulated DEGs were identified. The 118 DEGs were significantly correlated with diverse functions and pathways. The hub gene MUC1 had higher centrality scores in the PPI network, and the top 5 closely interacting hub genes, SLC7A11, AGR2, KRT18, CARTPT and TSPYL5, were identified. Conclusion: Our evidence suggests that the identified DEGs associated with F. nucleatum enhance our comprehension of the molecular Mechanisms underlying the tumorigenesis and development of CRC and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.展开更多
基金supported by the Natural Science Foundation of Shandong Province (No.ZR2022QC037)the Shandong Key R&D Program for Academician Team in Shandong (No.2023ZLYS02)+3 种基金the High-Level Talents Research Fund of Qingdao Agricultural University (No.663/1120033)the Young Experts of Taishan Scholars (No.201909130)the Shandong Technical System of Fish Industry (No.SDAIT-12-03)the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province (No.2019KJF003)。
文摘As a member of mucins family,MUC2 is an important component of mucus,which is characterized by tandem and irregular repeat sequences rich in threonine and serine.It is strongly expressed by goblet cells that are involved in innate immunity.Japanese flounder is an economically important marine flatfish.In this study,two homologous genes of MUC2 were identified,named MUC2-1 and MUC2-2.Depending on phylogenetic and structural analysis,MUC2-1 and MUC2-2 were clustered in two clades,respectively.Paralichthys olivaceus MUC2-1 showed a closer relationship with MUC2 in the higher vertebrates.Various healthy tissues were analyzed to determine the expression patterns,and both MUC2 genes showed high expression levels in the gills and intestines.Following Edwardsiella tarda challenge,P.olivaceus MUC2-1 and MUC2-2 both showed significant up-regulated expression in intestine and kidney.Moreover,MUC2-1 was significantly up-regulated in gill cell lines following PGN and polyI:C stimulation,and MUC2-2 was significantly up-regulated in gill cell lines following LPS stimulation.In addition,ISH results revealed that MUC2-1 and MUC2-2 showed the same tissue localization in intestine tissues,but displayed different localization in gill.The siRNA-mediated knockdown of MUC2-1 and MUC2-2 genes in the gill cell lines of Japanese flounder affected the expressions of galnt family genes and smad pathway members that are related to mucosal immunity.The results provided a valuable insight into understanding the functions of MUC2 on mucosal immune system in response to the invasion of bacterial pathogen.
文摘Background: Fusobacterium nucleatum can cause opportunistic and chronic infections and has recently been shown to be involved in colorectal cancer. However, the specific mechanism by which F. nucleatum induces colorectal carcinoma remains unclear. Methods: We downloaded the GSE110223, GSE110224, GSE113513 and GSE122183 microarray datasets from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) related to F. nucleatum in CRC by overlapping data sets was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome pathway (KEGG) analyses were used for enrichment analysis. Moreover, Cytoscape software constructed a protein-protein interaction (PPI) network of differentially expressed genes. Finally, western blot and RT-qPCR analysis identified the relative protein and mRNA expression of hub genes in the cell model. Results: In total, 118 DEGs in F. nucleatum-associated CRC were screened from nonoverlapping microarray data, among which 20 upregulated and 98 downregulated DEGs were identified. The 118 DEGs were significantly correlated with diverse functions and pathways. The hub gene MUC1 had higher centrality scores in the PPI network, and the top 5 closely interacting hub genes, SLC7A11, AGR2, KRT18, CARTPT and TSPYL5, were identified. Conclusion: Our evidence suggests that the identified DEGs associated with F. nucleatum enhance our comprehension of the molecular Mechanisms underlying the tumorigenesis and development of CRC and might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.