TISSUE & CELL
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2023
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IF 2.6
Yujun Zhao,Xiaotie Wang,Keke Nie
Background Osteoarthritis is a main cause of deformity in aging people. The chondrogenesis of human adipose-derived stem cells (hADSCs) has a positive effect on the cure of osteoarthritis. However, the regulatory mechanism of hADSC chondrogenesis still needs further exploration. This research investigates the role of interferon regulatory factor 1 (IRF1) in the chondrogenesis of hADSCs. Methods hADSCs were purchased and cultured. The interaction between IRF1 and hypoxia inducible lipid droplet associated (HILPDA) was predicted by bioinformatics analysis, and verified through dual-luciferase reporter and chromatin immunoprecipitation assays. The expressions of IRF1 and HILPDA in osteoarthritis cartilage samples were measured through qRT-PCR. After hADSCs were transfected or further induced for chondrogenesis, the chondrogenesis was visualized by Alcian blue staining, and the expressions of IRF1, HILPDA and chondrogenesis-related factors (SOX9, Aggrecan , COL2A1, MMP13, MMP3) were determined through qRT-PCR or Western blot . Results HILPDA bound to IRF1 in hADSCs. IRF1 and HILPDA levels were up-regulated during the chondrogenesis of hADSCs. Overexpressions of IRF1 and HILPDA promoted the chondrogenesis of hADSCs with the up-regulation of SOX9 , Aggrecan and COL2A1 and the down-regulation of MMP13 and MMP3 ; however, IRF1 silencing generated the opposite effects. Besides, HILPDA overexpression reversed the effects of IRF1 silencing on inhibiting chondrogenesis of hADSCs and regulating the expressions of chondrogenesis-related factors. Conclusion IRF1 promotes the chondrogenesis of hADSCs through up-regulating HILPDA level, providing novel biomarkers for treating osteoarthritis.
研究领域:
干细胞生物学
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Jiaxing Huang,Xiaotang Wang,Na Li,Wei Fan,Xingran Li,Qian Zhou,Jiangyi Liu,Wanqian Li,Zhi Zhang,Xiaoyan Liu,Shuhao Zeng,Hui Yang,Meng Tian,Peizeng Yang,Shengping Hou
Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation （CUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1 , and SEMA4D . In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.
研究领域:
免疫学
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神经科学
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分子生物学
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眼科学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
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2026
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IF 12.2
Liu Jiaxi,Miao Jiyu,Lv Yang,Fu Bingjie,Ren Xiaomin,Wang Naiqi,Xv Xuezhu,Gao Gongzhizi,Lin Zujie,Zhang Wenxiang,Zhao Bide,Shen Ying,Jia Yachun,Zhao Wanhong,Liu Rui,He Aili
Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled plasma cell proliferation and frequent therapeutic relapse. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic vulnerability in cancer. However, the mechanisms governing ferroptosis resistance in MM remain incompletely understood. Here, we identified thioredoxin (TXN), a central redox regulator, as a ferroptosis suppressor associated with poor prognosis in MM patients. Genetic knockdown or pharmacological inhibition of TXN impaired MM progression and enhanced ferroptosis-associated lipid peroxidation. Mechanistically, TXN suppression induced broad remodeling of polyunsaturated fatty acid-containing phospholipids (PUFA-PLs), particularly phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species enriched in ferroptosis-relevant PUFAs, thereby increasing ferroptosis susceptibility. Rescue experiments using a redox-deficient TXN mutant further demonstrated that the ferroptosis-suppressive function of TXN depends on its redox activity. We further identified interferon regulatory factor 1 (IRF1), which is downregulated in MM, as a transcriptional repressor of TXN. IRF1 depletion increased TXN expression and partially attenuated TXN deficiency-induced lipid peroxidation, supporting the functional relevance of the IRF1-TXN axis in ferroptosis regulation. In addition, bortezomib (BTZ)-resistant MM cells exhibited elevated TXN expression and reduced ferroptosis sensitivity. Targeting TXN restored ferroptotic vulnerability and enhanced BTZ sensitivity in MM cells. Collectively, our findings identify TXN as a critical suppressor of ferroptosis-associated phospholipid remodeling and lipid peroxidation in MM and establish the IRF1-TXN axis as a potential therapeutic target for overcoming ferroptosis resistance and improving MM treatment outcomes.
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DOI
高影响因子
Research
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2026
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IF 12.9
Lishi Jie,Jun Mao,Li Zhang,Houyu Fu,Xiaochen Li,Taiyang Liao,Yibao Wei,Deren Liu,Jiaojiao Du,Peng Wu,Songjiang Yin,Nongshan Zhang,Meng Cao,Peimin Wang
Knee osteoarthritis (KOA) is clinically characterized by recurrent and progressively worsening episodes;however, its underlying pathological mechanisms remain incompletely understood. Phenotypic changesand the specific migration of circulating monocytes may be key factors contributing to the recurrenceand progressive exacerbation of synovial inflammation in KOA. In this study, we report a specificsubtype of circulating monocytes in KOA that highly express IL1A, IL1R1, TNF, CXCL12, CXCL3,CXCL2, CCL20, and G0S2. These monocytes exhibit a trained immune phenotype, and their CXCR4-dependent migration to the synovium exacerbates synovial inflammation. HMGB1 (high mobility groupprotein B1) primes the trained immunity of this subtype, resulting in increased chromatin accessibility,and the transcriptional storage of multiple pro-inflammatory factors enables them to exhibit a morepositive inflammatory response when restimulated by HMGB1. In addition, we find that MyD88,downstream of HMGB1, recruits cytoplasmic IRF1 to the nucleus, and then stabilizes IRF1 in chromatinthrough SUMOylation of TRIM28 to exert transcriptional activity and epigenetic enhancement of pro-inflammatory factor expression. Finally, we found that KOA inflammation was effectively attenuated byblocking HMGB1. Taken together, this study reveals the mechanism by which trained immunity ofcirculating monocyte promote the progression of synovial inflammation, support a future therapeuticapproach in the management of KOA.Keywordsknee osteoarthritis; trained immunity; HMGB1; IRF1; SUMOylation; CXCL12; CXCR4
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DOI
高影响因子
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