BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to hum...BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.展开更多
The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it re...The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients.In this study,we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients.The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis.Using a structural–functional approach,we depicted the interface between 5A12 and CD147.This allowed us to identify two critical residues,Lys63 and Asp65,as potential targets for RA treatment,as the double mutation K63A/D65A inhibited Tm-cell activation,mimicking the neutralization by 5A12.This study provides not only a theoretical basis for a“CD147-Tm/Osteoclast-RA chain”for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.展开更多
文摘BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.
基金supported by grant(2015CB553704)from the National Basic Research Program of China,grants(2013ZX09301301 and 2014ZX09508002-002)+3 种基金from the National Science and Technology Major Project of China,grant(2017YFC0909002)from the National Key Research Project of China,grant(31470792)from the National Natural Science Foundation of China and grant(XDB08030102)from the Strategic Priority Research Program of the Chinese Academy of Sciences.
文摘The abnormal activation of CD4^(+)CD45RO+memory T(Tm)cells plays an important role in the pathogenesis of rheumatoid arthritis(RA).Previous studies have shown that CD147 participates in T-cell activation.However,it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients.In this study,we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients.The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis.Using a structural–functional approach,we depicted the interface between 5A12 and CD147.This allowed us to identify two critical residues,Lys63 and Asp65,as potential targets for RA treatment,as the double mutation K63A/D65A inhibited Tm-cell activation,mimicking the neutralization by 5A12.This study provides not only a theoretical basis for a“CD147-Tm/Osteoclast-RA chain”for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.
