C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement ...C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.展开更多
Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological roles.Type XIX collagen is a Fibril-Associated Collagen with Interrupted...Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological roles.Type XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this superfamily.This collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different tissues.The molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to NC6.The most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of cancer.Under physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in brain.Notwithstanding,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic properties.Type XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis patients.This novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.展开更多
目的探讨RNA传感器干扰素诱导的解旋酶C结构域蛋白1(interferon-induced helicase C domain protein 1,IFIH1)对人乳头瘤病毒18型(human papillomavirus 18,HPV18)阳性的人宫颈癌细胞HeLa增殖、迁移和侵袭的影响。方法利用GEPIA数据库分...目的探讨RNA传感器干扰素诱导的解旋酶C结构域蛋白1(interferon-induced helicase C domain protein 1,IFIH1)对人乳头瘤病毒18型(human papillomavirus 18,HPV18)阳性的人宫颈癌细胞HeLa增殖、迁移和侵袭的影响。方法利用GEPIA数据库分析IFIH1在正常宫颈组织和宫颈癌组织中的表达。Western blot检测IFIH1在C33A和HeLa细胞中的表达。将HPV18基因组转染到正常上皮细胞HaCaT中,并利用Western blot和实时定量PCR检测IFIH1的表达水平。利用实时无标记动态细胞分析技术和CCK8法检测细胞的增殖能力。划痕愈合实验、Transwell迁移实验和侵袭实验分别检测细胞的迁移能力和侵袭能力。Western blot和免疫荧光实验检测STAT3和磷酸化STAT3的蛋白表达和定位。结果GEPIA数据库分析显示IFIH1在宫颈癌组织中的表达量明显高于正常宫颈组织(P<0.05);相比于C33A细胞,HeLa细胞中IFIH1的表达水平明显增加(P<0.01);与正常HaCaT细胞相比,转染HPV18的HaCaT细胞中IFIH1的表达增加(P<0.01);与阴性对照相比,敲低IFIH1明显抑制HeLa细胞的增殖、迁移和侵袭能力,而过表达IFIH1则促进C33A细胞的增殖、迁移和侵袭(P<0.01);敲低IFIH1后,磷酸化STAT3蛋白的表达减少(P<0.01)。结论IFIHI在被HPV感染的宫颈癌细胞中表达增加,这将促进细胞的增殖、迁移和侵袭能力,可能与激活STAT3有关。展开更多
基金Acknowledgements This work was supported by the National Major Basic Research Program （No. 2004CB117401）；by the National Natural Science Foundation of China （No. 90408013）.
文摘C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.
基金supported by Institutode Salud Carlos Ⅲ(Grant PI17/00949)Fondo Europeode Desarrollo Regional(FEDER)“Una manera de hacer Europa” from the European Union+1 种基金Centrode Investigación Biomédicaen Redsobre Enfermedades Neurodegenerativas(CIBERNED-612)Fundación FEDER(Federación Espa?olade Enfermedades Raras),Consolidated Groupsfrom Gobiernode Aragón
文摘Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological roles.Type XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this superfamily.This collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different tissues.The molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to NC6.The most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of cancer.Under physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in brain.Notwithstanding,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic properties.Type XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis patients.This novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.
