Acta Pharmacologica Sinica最新文献

{"title":"Ginsenoside Rh2 in combination with IFNγ potentiated the anti-cancer effect by enhancing interferon signaling response in colorectal cancer cells.","authors":"Mu-Yang Huang, Chun-Cao Xu, Qian Chen, Yan-Ming Zhang, Wen-Yu Lyu, Zi-Han Ye, Ting Li, Ming-Qing Huang, Jin-Jian Lu","doi":"10.1038/s41401-025-01557-z","DOIUrl":"https://doi.org/10.1038/s41401-025-01557-z","url":null,"abstract":"<p><p>Interferon gamma (IFNγ) can amplify immune cell-mediated anti-tumor immunity, as well as directly kill cancer cells. Ginsenoside Rh2 (Rh2), a bioactive compound in traditional Chinese medicine, exhibits anti-cancer effects such as inhibiting proliferation and metastasis. Our earlier research found that Rh2 combined with IFNγ enhanced CXCL10 secretion in cancer cells. Here, we explored whether Rh2 and IFNγ exerted more potent anti-cancer activity in vitro and in vivo, along with its mechanisms and clinical value. Our data showed that Rh2 in combination with IFNγ resulted in a remarkably increased cytotoxicity in colorectal cancer cells including HT29, LoVo and T84 cell lines. Consistently, intratumoral injection with Rh2 plus IFNγ further restricted the HT29 tumor growth in vivo, and importantly, it was demonstrated to be safe for mice. Meanwhile, the combo treatment activated the stimulator of interferon genes (STING) pathway in cancer cells, promoting the transcription of downstream type I interferon. RNA sequencing revealed a dramatically transcriptional alteration in cancer cells with combo treatment and indicated that Rh2 further augmented the activation of interferon signaling pathway, compared with the IFNγ alone. Inhibition of janus kinase (JAK) by ruxolitinib could significantly rescue the cell death-triggered by the combo treatment. Then, a gene set named Rh2+IFNγ signature genes (RISG) was defined, which contained top 20 significantly upregulated genes from the combo treatment. Patients who exhibited a favorable response to the immunotherapy had a higher expression of RISG in tumor compared with those who did not respond. And the high expression of RISG was correlated with better clinical outcome in patients with colorectal cancer (CRC) and skin cutaneous melanoma (SKCM). Herein, the combination of Rh2 with IFNγ served as a promising strategy for cancer treatment, and its-derived RISG gene set also exhibited potential value in predicting clinical outcome. Schematic diagram of the anti-cancer effect of Rh2 combined with IFNγ. The schematic diagram illustrated that ginsenoside Rh2 in combination with IFNγ robustly activated the interferon signals in cancer cells, ultimately leading a significant cell death of cancer cells. ISGs, interferon-stimulated genes. Created with BioRender.com.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway.","authors":"Bai-En Liang, Luo-Sha Long, Xin-Yan Wu, Mei-Ying Huang, Ying Lai, Xi Yuan, Ming-Hui Wang, Meng Li, Qi-Qi Zheng, Hai-Ling Zhang, Man-Chun Chen, Zhen-de Liu, Xin Geng, Qian-Qian Lyu, Wei-Dong Wang, Qing-Hua Liu, Wei-Zhi Liu, Chun-Ling Li","doi":"10.1038/s41401-025-01545-3","DOIUrl":"https://doi.org/10.1038/s41401-025-01545-3","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and tubular injury. Alginate oligosaccharide (AOSC), a natural product obtained from alginate by acidolysis and hydrolysis, shows activities of antioxidant, immunomodulation, and anti-inflammation. In this study, we investigated the potential of AOSC in the treatment of AKI. Renal ischemia-reperfusion (I/R) was induced in male rats by clipping both the renal artery and vein for 45 min followed by reperfusion for 24 h. The rats were treated with AOSC (100 mg/kg, i.g.) before surgery. At the end of the experiments, both kidneys were collected for protein, mRNA measurement, or histological analysis. We showed that AOSC pretreatment significantly improved glomerular and tubular function in the kidney of I/R rats. AOSC markedly inhibited I/R-induced activation of TLR4/MyD88/NF-κB/IL-1β inflammatory signaling and prevented apoptosis in the kidney. In HK2 cells subjected to hypoxia/reoxygenation (H/R) stimulation, AOSC (250-1000 μg/ml) dose-dependently prevented pro-inflammatory responses and cell apoptosis. Transcriptomic analysis revealed that I/R increased the expression levels of mannose receptor type C1 (MRC1) in the kidney, which was markedly inhibited by AOSC. Molecular docking showed that AOSC interacted with E725, N727, E733, T743, S745, and N747 of MRC1 through hydrogen bonds. MRC1 gene knockout significantly improved renal function and attenuated I/R-induced kidney inflammation and apoptosis in mice. In line with this, AOSC failed to prevent I/R-induced kidney injury in MRC1 gene knockout mice. UPLC analysis showed that the protection of AOSC in HK2 cells subjected to H/R was likely attributed to MRC1-mediated intracellular endocytosis. In conclusion, AOSC prevents I/R-induced AKI, which is at least partially mediated by MRC1.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple and efficient method for purification of human pluripotent stem cell-derived cardiomyocytes via activating p53.","authors":"Peng Zhang, Sen-le Rao, Xiao-Chen Wang, Ping Liang, Ji-Zhen Lu, Wen-Wen Jia, Huang-Tian Yang","doi":"10.1038/s41401-025-01543-5","DOIUrl":"https://doi.org/10.1038/s41401-025-01543-5","url":null,"abstract":"","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cells in systemic lupus erythematosus: biology and traditional Chinese medicine therapy.","authors":"Ya-Nan Liang, Luo Chen, Qing-Yu Huang, Yu-Ting Song, Yu-Juan Fan, Tong-Qing Chen, Jia-Hui Ni, Dong Wang, Xiao-Yan Shen, Yi-Ming Wang, Yan You","doi":"10.1038/s41401-025-01554-2","DOIUrl":"https://doi.org/10.1038/s41401-025-01554-2","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by a progressive breakdown of immune tolerance to self-antigens, resulting in multiple tissue damage and clinical symptoms. Innate and adaptive immune cells including dendritic cells, macrophages, myeloid-derived suppressor cells (MDSCs), T cells and B cells are the key drivers in perpetuating and amplifying of this systemic disease. In this review we offer a comprehensive overview of recent advances in understanding the immune-pathogenesis of SLE with particular emphasis on regulatory immune cells exhibiting immunosuppressive properties, as well as newly identified factors influencing immune cell function and lineage differentiation. Furthermore, we discuss traditional Chinese medicine and natural extracts that have shown therapeutic effects on SLE by modulating immune cell differentiation and function, which may provide insights into their clinical applications.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSCLC cells sustain phase separation of cytoplasmic membrane-less organelles to protect themselves against cisplatin treatment.","authors":"Ning-Ning Li, Ling-Ling Rao, Dan Su, Bin-Hao Liu, Guo-Qiang Ma, Hong-Feng Wang, Zeng-Li Zhang, Zheng Ying","doi":"10.1038/s41401-025-01551-5","DOIUrl":"https://doi.org/10.1038/s41401-025-01551-5","url":null,"abstract":"<p><p>Cisplatin is the first platinum compound used for anticancer therapy, including non-small cell lung cancer (NSCLC). However, the clinical efficacy of cisplatin is strongly limited by cisplatin resistance. Hence, illuminating the mechanism of cisplatin resistance will aid in the development of therapeutic strategies that improve the sensitivity of cancer cells to cisplatin. Interestingly, membrane-less organelles, which are formed through biomolecular condensation in association with phase separation, have been recently linked with cancers. Here, we reveal a new molecular basis of cisplatin resistance in NSCLC, showing that cisplatin kills cancer cells by the alteration of cytoplasmic membrane-less organelles. Specifically, cisplatin treatment results in the disassembly of processing bodies (PBs) and the assembly of stress granule (SG)-like granules which are different from canonical SGs in NSCLC cells, but not cisplatin-resistant NSCLC cells. Moreover, alterations of PBs and noncanonical SG-like granules are associated with cisplatin-induced cancer cell death. Importantly, we found that disrupting PBs and canonical SGs with cycloheximide and FDA-approved pyrvinium helps cisplatin to kill cisplatin-resistant NSCLC cells. Taken together, our findings provide insight into the role of membrane-less organelle regulation in cisplatin resistance and offer an effective solution for overcoming cisplatin resistance in NSCLC.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexin 2 contributes to the protective effect of NAD⁺ on neuronal survival following neonatal hypoxia-ischemia.","authors":"Xiao-Wen Xu, Xiu-Wen Zhou, Li Zhang, Qing Wang, Xin-Xin Wang, Yi-Ming Jin, Li-Li Li, Mei-Fang Jin, Hai-Ying Wu, Xin Ding, Hong Ni","doi":"10.1038/s41401-025-01555-1","DOIUrl":"https://doi.org/10.1038/s41401-025-01555-1","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide (NAD) is a key coenzyme involved in cell metabolism associated with aging, cancer, neurodegenerative diseases and metabolic disorders. We recently showed that NAD⁺ therapy significantly improved neurobehavioral outcomes in neonatal mice after hypoxia-ischemia (HI), and bioinformatics analysis revealed that the expression of complexin 2 (CPLX2) in the injured cerebral cortex was significantly decreased 24 h after HI injury but could be reversed by NAD⁺ intervention. In this study we explored the role of CPLX2 in the survival and function of neonatal hypoxic-ischemic cortical neurons. HI models were established by permanent ligation of the left common carotid artery in mice. CPLX2-knockdown lentiviral vector was injected intraventricularly on postnatal day 1 (P1); CPLX2 knockout mice were also used. NAD⁺ (5 mg·kg^-1·d^-1, i.p.) was administered before HI surgery, thereafter once a day until sampling. We showed that NAD⁺ administration significantly ameliorated the morphological damages and neurobehavioral defects, and elevated the seizure thresholds in HI mice. All the beneficial effects of NAD⁺ were abolished by CPLX2 knockdown or knockout. In HT22 neuronal cells subjected to OGD/R, pretreated with NAD⁺ (100 μM) for 12 h significantly increased the cell viability, decreased the LDH levels, and inhibited the ferroptosis evidenced by the changes in redox-related parameters including concentrations of Fe²⁺, GSH, MDA, H₂O₂ as well as the expression of GPX4 and SLC7A11. CPLX2 knockdown in HT22 neuronal cells blocked the protective effects of NAD⁺ as in HI mice, whereas CPLX2 overexpression enhanced the inhibitory effects of NAD⁺ on ferroptosis in HT22 neuronal cells.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnane X receptor alleviates sepsis-induced liver injury through activation of yes-associated protein in mice.","authors":"Cheng-Hua Wu, Shuang Hu, Dan Li, Xiao-Wen Jiang, Hui Ou-Yang, Guo-Fang Bi, Peng Wang, Feng-Ting Liang, Wen-Hong Zhou, Xiao Yang, Jian-Hong Fang, Hui-Chang Bi","doi":"10.1038/s41401-025-01552-4","DOIUrl":"https://doi.org/10.1038/s41401-025-01552-4","url":null,"abstract":"<p><p>The severity of sepsis is attributed to excessive inflammatory responses leading to liver injury. Pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, has been implicated in regulating inflammation and liver regeneration. This study aimed to investigate the role of PXR in sepsis-induced liver injury and the underlying mechanisms. Sepsis models were established in mice, the mice were administered the typical mouse PXR agonist PCN (100 mg·kg^-1·d^-1, i.p.) for 3 consecutive days in advance, then subjected to CLP operation or LPS administration 1 h after the last administration of PCN. The results showed that PCN pretreatment significantly increased the survival rate of septic mice, while the survival rate was reduced after the knockout of Pxr. In addition, PCN pretreatment effectively alleviated sepsis-induced liver injury. In Pxr knockout mice, liver injury was more severe, whereas the protective effects of PCN pretreatment were abolished. Mechanistically, PCN pretreatment significantly upregulated the expression of yes-associated protein (YAP) and its downstream targets and decreased the level of phosphorylated nuclear factor-κB (NF-κB). Moreover, liver-specific knockdown of Yap blocked the protective effects of PCN pretreatment against sepsis-induced liver injury and downregulated the phosphorylation level of NF-κB. In summary, this study demonstrated that PXR activation protects against sepsis-induced liver injury through activation of the YAP signaling pathway, providing a new strategy for the diagnosis and treatment of sepsis-induced liver injury.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of machine learning and experimental validation reveals new lipid-lowering drug candidates.","authors":"Jing-Hong Chen, Ke-Xin Li, Chao-Fan Fan, Hong Yang, Zhi-Rou Zhang, Yi-Han Chen, Chang Qi, Ang-Hua Li, An-Qi Lin, Xin Chen, Peng Luo","doi":"10.1038/s41401-025-01539-1","DOIUrl":"https://doi.org/10.1038/s41401-025-01539-1","url":null,"abstract":"<p><p>Hyperlipidemia, a major risk factor for cardiovascular diseases, is associated with limitations in clinical lipid-lowering medications. Drug repurposing strategies expedite the research process and mitigate development costs, offering an innovative approach to drug discovery. This study employed systematic literature and guidelines review to compile a training set comprising 176 lipid-lowering drugs and 3254 non-lipid-lowering drugs. Multiple machine learning models were developed to predict the lipid-lowering potential of drugs. A multi-tiered validation strategy was implemented, encompassing large-scale retrospective clinical data analysis, standardized animal studies, molecular docking simulations and dynamics analyses. Through a comprehensive screening analysis utilizing machine learning, 29 FDA-approved drugs with lipid-lowering potential were identified. Clinical data analysis confirmed that four candidate drugs, with Argatroban as the representative, demonstrated lipid-lowering effects. In animal experiments, the candidate drugs significantly improved multiple blood lipid parameters. Molecular docking and dynamics simulations elucidated the binding patterns and stability of candidate drugs in interaction with related targets. We successfully identified multiple non-lipid-lowering drugs with lipid-lowering potential by integrating state-of-the-art machine learning techniques with multi-level validation methods, thereby providing new insights into lipid-lowering drugs, establishing a paradigm for AI-based drug repositioning research, and expanding the repertoire of lipid-lowering medications available to clinicians.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.","authors":"Jun-Ying Wang, Meng-Ping Chen, Jin-Xing Jiang, Yi-Ke Wan, Xin Li, Yi-Wei Zhang, Yi Fang, Hong-Hui Huang, Zhao-Yu Qin, Jian Hou","doi":"10.1038/s41401-025-01553-3","DOIUrl":"https://doi.org/10.1038/s41401-025-01553-3","url":null,"abstract":"<p><p>Selective nuclear export inhibitor selinexor (SEL) represents a promising therapeutic strategy for relapsed/refractory multiple myeloma (RRMM). But its mechanisms of action as well as factors that influence therapeutic responses have not been fully characterized yet. In this study we employed catTFRE proteomics technique to profile changes in nuclear abundance of activated transcription factors (TFs)/co-factors (TCs) in myeloma cells following SEL treatment. We found that pharmacological inhibition of exportin-1 (XPO1) by SEL leads to a significant nuclear accumulation of Lipin1 in NCI-H929 cells. Nuclear-localized Lipin1 acted as a transcriptional cofactor that suppressed the transcriptional activity of SREBPs. By performing subcellular localization analysis, molecular docking, co-immunoprecipitation and other assays, we demonstrated that Lipin1 was subjected to XPO1-dependent nuclear export. We demonstrated that SEL downregulated the expression of key lipogenesis-related genes regulated by SREBPs including FASN, SCD, DHCR24 and FDPS, leading to reduced fatty acid and cholesterol synthesis in MM cell lines and primary CD138⁺ cells. Using shRNA-mediated knockdown assays, we elucidated the critical role of Lipin1 in mediating the inhibitory effects of SEL on the SREBPs pathway and its contribution to SEL sensitivity both in vitro and in murine xenograft models. In conclusion, we reveal a novel mechanism by which SEL downregulates cellular lipid biosynthesis, thereby inhibiting the proliferation of myeloma cells. This study highlights the critical role of Lipin1 in the anti-myeloma effects of SEL, suggesting its potential as a biomarker for identifying patients who are most likely to benefit from SEL-based therapies.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JOSD2 alleviates acute kidney injury through deubiquitinating SIRT7 and negativity regulating SIRT7-NF-κB inflammatory pathway in renal tubular epithelial cells.","authors":"Ying Zhao, Qing-Qing Zhao, Shi-Jie Fan, Di-Yun Xu, Li-Ming Lin, Wu Luo, Bo-Zhi Ye, Chun-Peng Zou, Hong Zhu, Zai-Shou Zhuang, Yun-Jie Zhao, Guang Liang","doi":"10.1038/s41401-025-01546-2","DOIUrl":"https://doi.org/10.1038/s41401-025-01546-2","url":null,"abstract":"<p><p>Acute kidney injury (AKI), triggered by various stimuli including ischemia-reperfusion, nephrotoxic insult, and sepsis, is characterized by an abrupt deterioration in kidney function. Ubiquitination is a post-translational modification of proteins that plays a critical role in the pathogenesis and progression of AKI. In this study, we aimed to investigate the role and underlying mechanism of the deubiquitinating enzyme Josephin Domain-containing protein 2 (JOSD2) in AKI. We found that deficiency of JOSD2 exacerbated renal tubular injury and inflammation in AKI mice induced by cisplatin or ischemia-reperfusion injury. Conversely, the specific overexpression of JOSD2 in renal tubular epithelial cells effectively prevented renal tubular injury and inflammation induced in AKI mice. Mechanistically, we identified Sirtuin 7 (SIRT7) as a potential substrate of JOSD2 through mass spectrometry combined with co-immunoprecipitation analysis. JOSD2 removes the K63-linked ubiquitination of SIRT7 via its active site C24 and promotes P62-mediated autophagic degradation of SIRT7, which subsequently prevents the phosphorylation and nuclear translocation of P65 and reduces inflammatory responses in renal tubular epithelial cells. Our study reveals the role of the JOSD2-SIRT7 axis in regulating AKI-induced renal inflammation and highlights the potential of JOSD2 as a promising therapeutic target for AKI.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}