Autoimmunity最新文献

{"title":"SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19.","authors":"Alessandra Franco, Jaeyoon Song, Christina Chambers, Alessandro Sette, Alba Grifoni","doi":"10.1080/08916934.2023.2259133","DOIUrl":"10.1080/08916934.2023.2259133","url":null,"abstract":"<p><p>We enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (T_EM) and central memory T cells (T_CM). CD4+ CD25^high Treg expressed the chemokine receptor CCR6 in a considerable percentage, suggesting T cell homing to the vascular endothelium, lung and gut epithelial cells and brain. Treg phenotype was different than peripherally-induced Treg (pTreg) that revert from pro-inflammatory T cells under repeated stimulatory conditions, suggesting that SARS-CoV-2 spike-specific Treg differentiated from naïve T cells in tissues where the SARS-CoV-2 spike proteins were synthetized. Twenty two of 22 subjects studied responded to vaccination developing a spike-specific CD4+ T helper (Th)1 response, and 20 of 22 developing a spike-specific CD8+ cytotoxic T cells (CTL) response. However, in vaccine recipients the expansion of spike-specific pro-inflammatory T cells was less significant than the expansion of spike-specific Treg. Effector (T_EM) and central memory (T_CM) Treg were numerous as early as after two vaccine doses, with no significant differences following additional vaccine boosts. In co-culture experiments under stimulatory conditions, Treg regulated naïve T cell differentiation toward a pro-inflammatory phenotype and suppressed interferon (IFN)γ production by SARS-CoV-2-specific CD4 + Th1 cells.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cells-derived exosomes ameliorate high glucose and lipopolysaccharide-induced HPMECs injury through the Nrf2/HO-1 pathway","authors":"Hongyan Sun, Shitao Lu, Gaowei Qu, Junli Li, Bo Song","doi":"10.1080/08916934.2023.2290357","DOIUrl":"https://doi.org/10.1080/08916934.2023.2290357","url":null,"abstract":"Abstract Mesenchymal stem cells-derived exosomes (MSC-Exo) are considered to have great potential in the treatment of human diseases. However, the role of MSC-Exo in the process of diabetes with sepsis and the underlying molecular mechanism remain unclear. Human pulmonary microvascular endothelial cells (HPMECs) were treated with high glucose (HG) and lipopolysaccharide (LPS). Cell viability, migration, angiogenesis were analyzed by cell counting kit 8 assay, transwell assay and tube formation assay. Transmembrane electrical resistance (TER) detection and FITC-dextran assay were performed to evaluate cell barrier function. The protein levels of cell permeability-related markers, ferroptosis-related markers, exosomes-related markers, Nrf2 and HO-1 were examined using western bolt (WB) analysis. Besides, the levels of inflammation factors were tested by ELISA, and the levels of ferroptosis-related indicators were examined using corresponding assay kits. Flow cytometry was employed to analyze stem cell markers. The identification of MSC-Exo was performed using transmission electron microscopy, nanoparticle tracking analysis and WB analysis. DIO staining was used to examine the uptake of MSC-Exo by HPMECs. HG treatment suppressed HPMECs viability, migration, angiogenesis and TER, while promoted permeability, inflammation and ferroptosis. LPS treatment aggravated HG-induced HPMECs dysfunction, inflammation and ferroptosis. After HPMECs were co-cultured with MSC-Exo, cell injury induced by HG + LPS could be relieved. Moreover, MSC-Exo treatment enhanced the activity of Nrf2/HO-1 pathway in HG + LPS-induced HPMECs, and Nrf2-silenced MSC-Exo could promote HG + LPS-induced HPMECs injury. MSC-Exo alleviated HG + LPS-induced HPMECs injury via activating Nrf2/HO-1 pathway, confirming that it might be used for the treatment of diabetes with sepsis.","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138627691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0035796 depletion inhibits transforming growth factor-β1-induced pulmonary fibrosis in a miR-150-5p/L1CAM-dependent manner.","authors":"Juan Li, Xiaohong Chen, Baohong Zhang, Chenlu Wang","doi":"10.1080/08916934.2023.2250099","DOIUrl":"10.1080/08916934.2023.2250099","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of pulmonary fibrosis is not fully understood. Previous work has demonstrated the important role of circular RNA (circRNA) in pulmonary fibrosis development. This study aims to analyse the role of circ_0035796 in pulmonary fibrosis and the underlying mechanism.</p><p><strong>Methods: </strong>Human foetal lung fibroblast 1 (HFL1) cells were treated with transforming growth factor-β1 (TGF-β1) to mimic a pulmonary fibrosis cell model. The expression of circ_0035796, microRNA-150-5p (miR-150-5p) and L1 cell adhesion molecule (L1CAM) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of L1CAM, collagen I and fibronectin was detected by Western blot. Cell viability was analysed by CCK-8 assay. Cell proliferation, invasion and migration were investigated by 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell invasion assay and wound-healing assay, respectively. The secretion of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) was analysed by Enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by detecting Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) level using commercial kits. The association of miR-150-5p with circ_0035796 and L1CAM was identified by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay.</p><p><strong>Results: </strong>Circ_0035796 and L1CAM expression were dramatically upregulated, while miR-150-5p expression was downregulated in TGF-β1-treated HFL1 cells. TGF-β1 treatment induced cell proliferation, migration, invasion, IL-6 and TNF-α secretion, and oxidative stress, whereas circ_0035796 depletion relieved these effects. In addition, circ_0035796 acted as a sponge of miR-150-5p and miR-150-5p combined with L1CAM. Moreover, miR-150-5p depletion attenuated circ_0035796 knockdown-mediated effects in TGF-β1-exposed HFL1 cells. The regulation of miR-150-5p on TGF-β1-induced fibroblast activation involved the downregulation of L1CAM. Further, circ_0035796 modulated L1CAM expression by interacting with miR-150-5p in TGF-β1-exposed HFL1 cells.</p><p><strong>Conclusion: </strong>Circ_0035796 knockdown ameliorates TGF-β1-induced pulmonary fibrosis through the miR-150-5p/L1CAM axis <i>in vitro</i>.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41189667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic tumour-derived exosomal miR-1225-5p regulates M2 macrophage polarisation via toll-like receptor 2 to promote ovarian cancer progress.","authors":"Shu Tan, Hao Yu, Zhaocong Zhang, Yiming Liu, Ge Lou","doi":"10.1080/08916934.2023.2281226","DOIUrl":"10.1080/08916934.2023.2281226","url":null,"abstract":"<p><p>Tumor-secreted exosomes are critical for the functional regulation of tumor-associated macrophages (TAMs). This study aimed to explore how exosomes secreted by ovarian carcinoma cells regulate the phenotype and function of macrophages. Hypoxic treatment of A2780 cells was postulated to mimic the tumor microenvironment, and exosomes were co-cultured with TAMs. miR-1225-5p was enriched in hypoxic exosomes and contributed to M2 macrophage polarizationby modulating Toll-like receptor 2 expression (TLR2). Furthermore, hypoxia-treated macrophages promote ovarian cancer cell viability, migration, and invasion via the wnt/β-catenin pathway. This study clarified that exosomal miR-1225-5p promotes macrophage M2-like polarization by targeting TLR2 to promote ovarian cancer, which may via the wnt/β-catenin pathway.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role of ceRNA network in B lymphocytes of patients with immune thrombocytopenia.","authors":"Xin He, Nianbin Li, Donglan Liu, Mengtong Zang, Manjun Zhao, Ningyuan Ran, Chunyan Liu, Limin Xing, Huaquan Wang, Ting Wang, Zonghong Shao","doi":"10.1080/08916934.2023.2281225","DOIUrl":"10.1080/08916934.2023.2281225","url":null,"abstract":"<p><strong>Objective: </strong>High-throughput sequencing was used to screen expressing differences of miRNA, lncRNA, and mRNA in CD19+ B peripheral blood samples of newly diagnosed immune thrombocytopenia (ITP) patients and healthy controls. The study aimed to explore the regulatory role of ceRNA network in the pathogenesis of dysfunctional CD19 + B lymphocytes of ITP patients.</p><p><strong>Methods: </strong>CD19+ B lymphocytes were isolated from peripheral blood samples of ITP patients and their healthy counterparts. High-throughput sequencing was used to screen for the expression of miRNA, lncRNA, and mRNA of ITP patients and healthy controls, which were analysed by the ceRNA network. Moreover, qPCR was used to verify the differential expression of miRNA, lncRNA, and mRNA in ITP patients and healthy controls. The correlation between differentially expressed miRNA, lncRNA, mRNA, and B lymphocyte subsets was also analysed.</p><p><strong>Results: </strong>The CD19+ B lymphocytes of 4 newly diagnosed ITP patients and 4 healthy controls were sequenced and analysed. There were 65 differentially expressed lncRNA and 149 mRNA forming a ceRNA network showed that 12 lncRNA and 136 differentially expressed mRNA were closely associated. Similarly, miR-144-3p, miR-374c-3p, and miR-451a were highly expressed in ITP patients, as confirmed by qPCR, which was consistent with the high-throughput sequence results. LOC102724852 and CCL20 were highly expressed in ITP patients, while LOC105378901, LOC112268311, ALAS2, and TBC1D3F were not as compared to healthy controls, which was consistent with the high-throughput sequence results. In addition, the expression of miR-374c-3p, LOC112268311, LOC105378901, and CXCL3 were correlated with the percentage of B lymphocyte subsets.</p><p><strong>Conclusions: </strong>The ceRNA network of miRNA, lncRNA, and mRNA in peripheral CD19 + B lymphocytes plays an essential role in the pathogenesis of ITP.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Agmatine on a mouse model of allergic airway inflammation: A comparative study.","authors":"Mohammed K Еlmahdy,&nbsp;Rania R Abdelaziz,&nbsp;Hoda S Elmahdi,&nbsp;Ghada M Suddеk","doi":"10.1080/08916934.2022.2093864","DOIUrl":"https://doi.org/10.1080/08916934.2022.2093864","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a chronic lung disease that injures and constricts the airways. This study evaluates the effects of agmatine on ovalbumin (OVA)-induced allergic inflammation of the airways.</p><p><strong>Methods: </strong>OVA sensitization by intraperitoneal injection was used to induce airway inflammation in mice on days 0 and 7; then the mice were challenged using beclomethasone (150 µg/kg, inhalation), a standard anti-asthmatic drug, from day 14 to day 16. Furthermore, agmatine (200 mg/kg) was intraperitoneally injected on day 0 and then daily for 16 days, followed by OVA challenge. The lung weight ratio, total and differential cell counts, TNF-α, interleukin-5 (IL-5) and IL-13 in bronchoalveolar lavage fluid (BALF), lung nitrite/nitrate (NO), and oxidative parameters were determined. Moreover, histopathological and immunohistochemical staining was employed.</p><p><strong>Results: </strong>Injection of agmatine (200 mg/kg) for 16 days significantly attenuated inflammation of the airways. The levels of BALF inflammatory cells, TNF-α, IL-5, IL-13, lung NO, and malondialdehyde (MDA), significantly decreased with concomitant elevation of superoxide dismutase (SOD) levels. Histological and immunohistochemical analyses of mast cells paralleled to biochemical improvements.</p><p><strong>Conclusion: </strong>Finally, this study illustrated that agmatine attenuates the allergic inflammation of airways caused by OVA by mitigating cytokines release, NO expression, and oxidative stress.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down-regulation of <i>KLF9</i> ameliorates LPS-caused acute lung injury and inflammation in mice via reducing <i>GSDMD</i> expression.","authors":"Renliang Qu,&nbsp;Jingjing Liu,&nbsp;Lili Feng,&nbsp;Lianbing Li,&nbsp;Junwei Liu,&nbsp;Fengnan Sun,&nbsp;Lin Sun","doi":"10.1080/08916934.2022.2114465","DOIUrl":"https://doi.org/10.1080/08916934.2022.2114465","url":null,"abstract":"<p><p>Acute lung injury (ALI) is considered as a severe respiratory disease with aggravated inflammatory responses. Krüppel-like factor 9 (<i>KLF9</i>), a member of KLF family, has been reported to be involved in inflammatory disorders. However, the effect of <i>KLF9</i> in ALI has not been elucidated. Here the present study was to clarify the role of <i>KLF9</i> and its mechanism in ALI. The ALI <i>in vitro</i> model was established with lipopolysaccharide (LPS)-treated RAW264.7 cells. Mice were injected with LPS to conduct an ALI <i>in vivo</i> model. The expression of <i>KLF9</i> and gasdermin D (<i>GSDMD</i>) was examined using quantitative reverse transcription-PCR, haematoxylin-eosin/immunohistochemistry staining and western blot assays. Enzyme-linked immunosorbent assay was employed to detect the levels of inflammatory cytokines. JASPAR database was used to predict the recognition motif of <i>KLF9</i>, and the relationship between <i>KLF9</i> and <i>GSDMD</i> was determined by luciferase reporter assay and chromatin immunoprecipitation analysis. The number of neutrophils in bronchoalveolar lavage fluid as well as the wet/dry weight ratio was caculated. The results showed that The expression of <i>KLF9</i> in lung was significantly increased in LPS-stimulated mice. Moreover, <i>KLF9</i> knockout relieved the lung injury in ALI mice. <i>GSDMD</i> is one of targets genes of the transcription factor <i>KLF9</i>. <i>KLF9</i> knockout induced a decreased expression of <i>GSDMD</i> in LPS-treated mice. Furthermore, in RAW264.7 cells after LPS administration, <i>KLF9</i> knockdown reduced the levels of inflammatory factors and suppressed the expression of <i>GSDMD</i>. In summarise, these findings exhibited that <i>KLF9</i> knockout could mitigate the lung injury and inflammatory responses in ALI mice by directly regulating <i>GSDMD</i>.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis.","authors":"Yuchang Zhang,&nbsp;Ping Zhao,&nbsp;Sen Li,&nbsp;Xiangqian Mu,&nbsp;Huaqi Wang","doi":"10.1080/08916934.2022.2103798","DOIUrl":"https://doi.org/10.1080/08916934.2022.2103798","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression.</p><p><strong>Methods: </strong>Levels of circSCAPER, miR-127-5p and toll-like receptor 4 (TLR4) were detected by qRT-PCR or western blotting. Cell apoptosis was determined by flow cytometry. The expression of Aggrecan and Matrix metallopeptidase was examined using western blot to assess extracellular matrix (ECM) degradation. Inflammatory response and oxidative stress were determined by measuring the release of inflammatory factors, along with the generation of intracellular reactive oxygen species and malondialdehyde. The interaction between miR-127-5p and circSCAPER or TLR4 was determined by dual-luciferase reporter, RNA immunoprecipitation and pull-down assays.</p><p><strong>Results: </strong>Chondrocytes were treated with interleukin-1β (IL-1β) to mimic OA condition in vitro. CircSCAPER was increased in OA cartilages and IL-1β-induced chondrocytes. Functionally, knockdown of circSCAPER attenuated IL-1β-evoked apoptosis, ECM degradation, inflammation and oxidative stress in vitro. CircSCAPER up-regulation in OA cartilages was discovered to be accompanied by decreased miR-127-5p and increased TLR4. Mechanistically, circSCAPER acted as a sponge for miR-127-5p to positively regulate TLR4 expression in chondrocytes. IL-1β treatment reduced miR-127-5p expression but up-regulated TLR4 expression, re-expression of miR-127-5p suppressed IL-1β-caused chondrocyte injury, which was abolished by TLR4 overexpression. Moreover, miR-127-5p inhibition reversed the protective action of circSCAPER knockdown on chondrocytes under IL-1β treatment.</p><p><strong>Conclusion: </strong>CircSCAPER silencing protected against IL-1β-induced apoptosis, ECM degradation, inflammation and oxidative stress in chondrocytes via miR-127-5p/TLR4 axis.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria as a key player in systemic lupus erythematosus.","authors":"Diana C Quintero-González,&nbsp;Marcela Muñoz-Urbano,&nbsp;G Vásquez","doi":"10.1080/08916934.2022.2112181","DOIUrl":"https://doi.org/10.1080/08916934.2022.2112181","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a heterogeneous, multisystemic autoimmune disease with a broad clinical spectrum. Loss of self-tolerance and chronic inflammation are critical markers of SLE pathogenesis. Although alterations in adaptive immunity are widely recognized, increasing reports indicate the role of mitochondrial dysfunction in activating pathogenic pathways involving the innate immune system. Among these, disarrangements in mitochondrial DNA copy number and heteroplasmy percentage are related to SLE activity. Furthermore, increased oxidative stress contributes to post-translational changes in different molecules (proteins, nucleic acids, and lipids), release of oxidized mitochondrial DNA through a pore of voltage-dependent anion channel oligomers, and spontaneous mitochondrial antiviral signaling protein oligomerization. Finally, a reduction in mitophagy, apoptosis induction, and NETosis has been reported in SLE. Most of these pathways lead to persistent and inappropriate exposure to oxidized mitochondrial DNA, which can stimulate plasmacytoid dendritic cells, enhance autoreactive lymphocyte activation, and release increased amounts of interferons through stimulation of toll-like receptors and cytosolic DNA sensors. Likewise, abnormal T-cell receptor activation, decreased regulatory T cells, enhanced Th17 phenotypes, and increased monocyte maturation to dendritic cells have also been observed in SLE. Targeting the players involved in mitochondrial damage can ultimately help.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40718291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of MKL1 ameliorates oxidative stress-induced chondrocyte apoptosis and cartilage matrix degeneration by activating TWIST1-mediated PI3K/AKT signaling pathway in rats.","authors":"Chao Wan,&nbsp;Wei Liu,&nbsp;Limin Jiang,&nbsp;Shengjie Dong,&nbsp;Weihua Ma,&nbsp;Shijun Wang,&nbsp;Dan Liu","doi":"10.1080/08916934.2022.2114466","DOIUrl":"https://doi.org/10.1080/08916934.2022.2114466","url":null,"abstract":"<p><p>Studies have reported that megakaryocytic leukemia 1 (MKL1) is closely related to the pathological process of a variety of inflammatory diseases, but its role in osteoarthritis (OA) needs to be clarified. This study aimed to investigate the regulatory role of MKL1 in oxidative stress-induced chondrocyte apoptosis and cartilage matrix degeneration. The expressions of target mRNAs and proteins were measured by using reverse transcription-quantitative polymerase chain reaction and western blotting. ELISA assay was used to measure the levels of IL-6, IL-8, and TNF-α in chondrocytes. And commercial kits based on different spectrophotometry or colorimetry methods were performed to validate oxidative stress. CCK-8 and apoptosis kits were used to determine cell viability and apoptosis. Rat OA model was established by anterior cruciate ligament transection (ACLT), and the expression of MKL1 was interfered by injecting sh-MKL1 lentiviral vector into caudal vein. The results showed that the expression of MKL1was induced by H₂O₂ in chondrocytes. Knockdown of MKL1 alleviated H₂O₂-induced inflammation and cell apoptosis, reduced H₂O₂-induced oxidative stress, and improved cartilage matrix degeneration of chondrocytes. Besides, inhibition of MKL1 regulated the activation of TWIST1-mediated PI3K/AKT signaling. Further studies have found that TWIST1-mediated PI3K/AKT signaling was involved in the regulation mechanism of MKL1 on chondrocyte apoptosis and cartilage matrix degeneration. Next, intervention with MKL1 inhibited the progression of OA in rats. These results demonstrated that MKL1 regulate the apoptosis and cartilage matrix degeneration of chondrocytes via TWIST1-mediated PI3K/AKT signaling.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}