纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐...纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐明。本文综述了S100A9在肺、肝、肾、心脏及皮肤等主要纤维化疾病中的研究进展,重点探讨其在细胞信号通路、免疫调节及炎症反应中的作用,旨在为纤维化疾病的诊断和治疗提供新的研究思路。Fibrosis is the terminal stage of various chronic diseases, characterized by excessive accumulation of fibrous connective tissue in tissues, leading to organ structural damage and loss of function. As an important member of the S100 protein family, the role of S100A9 in various inflammatory diseases and cancers has been widely studied, but its role and mechanism in fibrotic diseases have not been fully elucidated. This article reviews the research progress of S100A9 in major fibrotic diseases such as lung, liver, kidney, heart, and skin, with a focus on exploring its role in cellular signaling pathways, immune regulation, and inflammatory response, aiming to provide new research ideas for the diagnosis and treatment of fibrotic diseases.展开更多
Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Alt...Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.展开更多
●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in spe...●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.展开更多
文摘纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐明。本文综述了S100A9在肺、肝、肾、心脏及皮肤等主要纤维化疾病中的研究进展,重点探讨其在细胞信号通路、免疫调节及炎症反应中的作用,旨在为纤维化疾病的诊断和治疗提供新的研究思路。Fibrosis is the terminal stage of various chronic diseases, characterized by excessive accumulation of fibrous connective tissue in tissues, leading to organ structural damage and loss of function. As an important member of the S100 protein family, the role of S100A9 in various inflammatory diseases and cancers has been widely studied, but its role and mechanism in fibrotic diseases have not been fully elucidated. This article reviews the research progress of S100A9 in major fibrotic diseases such as lung, liver, kidney, heart, and skin, with a focus on exploring its role in cellular signaling pathways, immune regulation, and inflammatory response, aiming to provide new research ideas for the diagnosis and treatment of fibrotic diseases.
基金supported by the National Key Research and Development Program of China(No.2023YFC2506504)the National Natural Science Foundation of China(No.82370255,and No.U24A20646)the Shanghai Science and Technology Commission Project(No.23410761200).
文摘Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.
基金Supported by Regional Science Foundation Project of the National Natural Science Foundation of China(No.82060827,No.82260891)The Key Discipline of Universities in the“14th Five-Year Plan”Autonomous Region-Traditional Chinese Medicine at Xinjiang Medical University.
文摘●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.
