Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"A dual sensing mechanism of eastern honeybee Apis cerana that upregulates the expression level of chemosensory protein CSP1 and enhances the binding affinity to loquat floral volatiles at low temperature","authors":"Jia-Qi Huang ,&nbsp;Li Zhang ,&nbsp;Fan Wu ,&nbsp;Jing Tan ,&nbsp;Ping Wen ,&nbsp;Wei Xu ,&nbsp;Hong-Liang Li","doi":"10.1016/j.bbadis.2024.167601","DOIUrl":"10.1016/j.bbadis.2024.167601","url":null,"abstract":"<div><div>As a native bee species, the eastern honeybee (<em>Apis cerana</em>) plays an essential role in pollinating loquat flowers, which bloom in early winter in China. This pollination behavior is closely related to <em>A. cerana</em>'s ability to adapt to low temperatures, which depends on the functionality of its chemoreceptive system. Transcriptome analysis revealed a significant upregulation of the <em>A. cerana</em> chemosensory protein 1 (CSP1) gene at low temperatures. Fluorescence competitive binding experiments indicated that nine chemical volatiles from loquat flowers exhibited a stronger binding affinity to CSP1 than to odorant binding protein 2 (OBP2). Thermodynamic analysis revealed that CSP1's binding affinity increases at low temperatures, with a static binding mechanism largely influenced by the specific volatile molecule rather than the type of olfactory soluble protein. Molecular docking and site-directed mutagenesis confirmed that F44 residue may play a key role in CSP1's binding to three primary volatile compounds. In summary, the present study identified a dual sensing mechanism in which low temperatures upregulated the expression of CSP1 and enhanced the binding affinity of CSP1 to loquat flower volatiles. These findings not only clarify <em>A. cerana</em>'s chemoreceptive mechanism toward loquat flower volatiles in pollination but also provide a theoretical basis for further exploring ecological adaptations between native bees and early-winter flowering plants.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167601"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP13 inhibition exacerbates mitochondrial dysfunction and acute kidney injury by acting on MCL-1","authors":"Qian Wang ,&nbsp;Shihan Cao ,&nbsp;Zhenzhen Sun ,&nbsp;Wenping Zhu ,&nbsp;Le Sun ,&nbsp;Yuanyuan Li ,&nbsp;Dan Luo ,&nbsp;Songming Huang ,&nbsp;Yue Zhang ,&nbsp;Weiwei Xia ,&nbsp;Aihua Zhang ,&nbsp;Zhanjun Jia","doi":"10.1016/j.bbadis.2024.167599","DOIUrl":"10.1016/j.bbadis.2024.167599","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a globally recognized public health issue that lacks satisfactory therapeutic strategies. Deubiquitinase ubiquitin-specific protease 13 (USP13) regulates various pathophysiological processes via the deubiquitination of multiple substrates. However, its role in AKI remains unclear. To illustrate the role and underlying mechanism of USP13 in AKI, we subjected <em>Usp13</em> knockdown mice, and mice treated with the USP13 inhibitor spautin-1, and mice with USP13 overexpression plasmids to cisplatin challenge. Renal tubular epithelial cell injury and mitochondrial disturbances were determined in vitro. Immunoprecipitation and deubiquitylation assays were performed to verify the interactions between USP13 and myeloid cell leukemia (MCL-1). We observed a significant decrease of USP13 expression in cisplatin-challenged AKI mice and renal tubular epithelial cells. Overexpression of USP13 alleviated kidney injury, whereas knockdown or inhibition of USP13 further exacerbated AKI. Mechanistically, USP13 downregulation resulted in increased degradation of MCL-1 which is a key regulator of cell survival and mitochondrial function, and the resultant MCL-1 reduction disrupted mitochondrial homeostasis and aggravated renal tubular epithelial cell injury and death, contributing to AKI progression. In conclusion, our findings demonstrated that inhibition of USP13 could exacerbate mitochondrial dysfunction and AKI through its effects on MCL-1, and USP13 may serve as a target for AKI prevention and treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167599"},"PeriodicalIF":4.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confrontation with kidney inflammation through a HMGB1-targeted peptide augments anti-fibrosis therapy","authors":"Yuanjun Deng ,&nbsp;Tianjing Zhang ,&nbsp;Yang Cai ,&nbsp;Lin Ke ,&nbsp;Xi He ,&nbsp;Chunjiang Zhang ,&nbsp;Lele Liu ,&nbsp;Qian Li ,&nbsp;Yixuan Zhao ,&nbsp;Gang Xu ,&nbsp;Min Han","doi":"10.1016/j.bbadis.2024.167586","DOIUrl":"10.1016/j.bbadis.2024.167586","url":null,"abstract":"<div><div>Damage to the renal tubular epithelial cells (TEC) is a key cellular event in kidney inflammation and subsequent fibrosis. However, drugs targeting renal TEC (RTEC) are limited to the alleviation of kidney fibrosis. Lethal giant larvae 1 (Lgl1) plays a key role in epithelial cell polarity and proliferation. Here, we report that the renal tubule epithelial-specific deletion of Lgl1 significantly ameliorated intrarenal inflammation and kidney fibrosis. Mechanistically, Lgl1 suppressed the activity of the deacetylase sirtuin 1 (SIRT1) and augmented the acetylation of high-mobility group box 1 (HMGB1) at the lysine 90 (K90) site. Consequently, HMGB1 migrated from the nucleus to the cytoplasm, activating an inflammatory cascade. Our renoprotective strategy was to construct a mimic peptide, TAT-K90WT, that targets HMGB1 K90 acetylation. Administration of this peptide significantly ameliorated inflammation and fibrosis in the kidneys. In summary, the Lgl1-HMGB1 axis plays an important role in renal fibrosis, and targeting HMGB1 acetylation by mimicking peptides is a potential strategy to prevent fibrosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167586"},"PeriodicalIF":4.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish in-vivo study reveals deleterious activity of human TBC1D24 genetic variants linked with autosomal dominant hearing loss","authors":"A. Sarosiak ,&nbsp;J. Jędrychowska ,&nbsp;D. Oziębło ,&nbsp;N.S. Gan ,&nbsp;N. Bałdyga ,&nbsp;M.L. Leja ,&nbsp;T. Węgierski ,&nbsp;I.A. Cruz ,&nbsp;D.W. Raible ,&nbsp;H. Skarżyński ,&nbsp;P. Tylzanowski ,&nbsp;V. Korzh ,&nbsp;M. Ołdak","doi":"10.1016/j.bbadis.2024.167598","DOIUrl":"10.1016/j.bbadis.2024.167598","url":null,"abstract":"<div><div>Hearing loss is a common sensory impairment with a heterogeneous genetic etiology. Genetic variants in the <em>TBC1D24</em> gene have recently emerged as an important cause of the non-syndromic autosomal dominant hearing loss (ADHL). However, the molecular mechanism behind the <em>TBC1D24</em>-associated ADHL is unknown. Using a zebrafish model, we investigated involvement of <em>TBC1D24</em> in hearing and the functional effects of the associated ADHL-causing genetic variants. We show that the morpholino-mediated knockdown of Tbc1d24 resulted in defective ear kinocilia structure and reduced locomotor activity of the embryos. The observed phenotypes were rescued by a wild-type <em>TBC1D24</em> mRNA but not by a mutant mRNA carrying the ADHL-causing variant c.553G &gt; A (p.Asp185Asn), supporting its pathogenic potential. CRISPR-Cas9-mediated knock-out of <em>tbc1d24</em> led to mechanosensory deficiency of lateral line neuromasts. Overexpression of <em>TBC1D24</em> mRNA resulted in developmental abnormalities associated with ciliary dysfunction and mesendodermal mispatterning. We observed that the ADHL-causing <em>TBC1D24</em> variants: c.553G &gt; A (p.Asp185Asn); c.1460A&gt;T (p.His487Leu), c.1461C &gt; G (p.His487Gln) or a novel variant c.905 T &gt; G (p.Leu302Arg) alleviated the effect of overexpression, indicating that these variants disrupt the TBC1D24 function. Furthermore, the zebrafish phenotypes correspond to the severity of ADHL. Specific changes in ear structures upon <em>TBC1D24</em> overexpression further highlighted its tissue-specific role in ciliary function and inner ear development. Our findings provide functional evidence for the pathogenic potential of the ADHL-causing <em>TBC1D24</em> variants and lead to new insights into the function of <em>TBC1D24</em> in cilia morphogenesis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167598"},"PeriodicalIF":4.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic alcohol consumption exacerbates ischemia-associated skeletal muscle mitochondrial dysfunction in a murine model of peripheral artery disease","authors":"Emma Fletcher ,&nbsp;Dimitrios Miserlis ,&nbsp;Evlampia Papoutsi ,&nbsp;Jennifer L. Steiner ,&nbsp;Bradley Gordon ,&nbsp;Gleb Haynatzki ,&nbsp;Pal Pacher ,&nbsp;Panagiotis Koutakis","doi":"10.1016/j.bbadis.2024.167584","DOIUrl":"10.1016/j.bbadis.2024.167584","url":null,"abstract":"<div><h3>Purpose</h3><div>Peripheral artery disease (PAD) causes ischemic mitochondriopathy-associated muscle damage, amplifying patient disability and mortality. Although alcohol and a high-fat diet enhance PAD predisposition and severity, their impact on PAD myopathy is unclear. Using our murine model of PAD, we investigated the combined effect of chronic alcohol and fat consumption on intramuscular oxidative stress and mitochondrial content, function, and quality control. The potential relationship between intramuscular aldehyde dehydrogenase 2 (ALDH2) content, oxidative stress and mitochondriopathy was also explored.</div></div><div><h3>Methods</h3><div>Twenty-four male, 24 female, 8-month-old C57BL/6 J mice received high-fat-sucrose (HFS) or low-fat-sucrose (LFS) diets for 16-weeks, followed by either 20 % ethanol (EtOH) supplemented in the drinking water or continued water access for another 12-weeks (<em>n</em> = 12 mice/4 groups). The left femoral artery was ligated to induce hindlimb ischemia (HLI), and mice 4-weeks post-ligation were euthanized.</div></div><div><h3>Results</h3><div>Chronic HLI was associated with an ischemic muscle mitochondriopathy, which was exacerbated by concurrent HFS and EtOH feeding. Intramuscular ALDH2 was also reduced in mice consuming HFS + EtOH, particularly in the ischemic limb, but increased in their LFS + EtOH-consuming counterparts. Moreover, reduced ALDH2 was strongly correlated with markers of oxidative stress and mitochondrial dysfunction.</div></div><div><h3>Conclusions</h3><div>ALDH2 could be a promising therapeutic target to optimize intramuscular mitochondrial function in PAD patients, particularly those who habitually consume a diet high in fat and alcohol.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167584"},"PeriodicalIF":4.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinate dehydrogenase mediated ROS production contributes to ASIC1a-induced chondrocyte pyroptosis in rheumatoid arthritis","authors":"Wenqiang Liu ,&nbsp;Yayun Xu ,&nbsp;Weirong Hu ,&nbsp;Longbiao Zhang ,&nbsp;Cheng Wang ,&nbsp;Fengshuo Wang ,&nbsp;Zhuoyan Zai ,&nbsp;Xuewen Qian ,&nbsp;Xiaoqing Peng ,&nbsp;Feihu Chen","doi":"10.1016/j.bbadis.2024.167585","DOIUrl":"10.1016/j.bbadis.2024.167585","url":null,"abstract":"<div><div>Our previous study showed that acidic stimuli activate acid-sensitive ion channel 1a (ASIC1a), resulting in chondrocyte destruction associated with rheumatoid arthritis (RA). However, the exact underlying processes remain unclear. Recent evidence suggests that the production of reactive oxygen species (ROS) mediated by succinate dehydrogenase (SDH), contributes to chondrocyte damage. The objective of this study was to investigate the involvement of SDH in ASIC1a-induced chondrocyte destruction in RA and to explore the associated mechanisms both <em>in vivo</em> and <em>in vitro</em>. Our findings revealed that the cartilage of mice with collagen-induced arthritis (CIA) and acid-treated chondrocytes exhibited a substantial increase in SDH expression. Furthermore, SDH inhibition attenuates acidosis-induced pyroptosis in chondrocytes. Notably, ASIC1a activation through acid stimuli increases SDH activity and pyroptosis through the Ca²⁺/CaMKK2/AMPK pathway in chondrocytes. Mechanistically, SDH assembly factor 2 (SDHAF2) was identified as a key modulator of SDH activity induced by ASIC1a in acid-stressed chondrocytes. Moreover, the expression of SDH in CIA mouse chondrocytes decreased and the histological characteristics of ankle joint damage were reduced by the ASIC1a-particular blocker PcTx-1. Overall, these observations suggest that ASIC1a activation under acidic conditions increases SDH activity and modulates SDHAF2, thereby promoting chondrocyte pyroptosis through the Ca²⁺/CaMKK2/AMPK pathway.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167585"},"PeriodicalIF":4.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sports training improves motor function after spinal cord injury by regulating microtubule dynamics","authors":"Yue Tang ,&nbsp;Xiaohuan Wang ,&nbsp;Mengjie Huang ,&nbsp;Yijie Li ,&nbsp;Xiaoxie Liu ,&nbsp;Hong Zeng ,&nbsp;Yanyan Yang ,&nbsp;Mouwang Zhou","doi":"10.1016/j.bbadis.2024.167587","DOIUrl":"10.1016/j.bbadis.2024.167587","url":null,"abstract":"<div><div>Spinal cord injury (SCI) often results in persistent disabilities, primarily due to deficient axon regeneration and irreversible neuronal loss. Sports training is a widely adopted intervention in clinical practice and research to promote axonal sprouting and synaptic plasticity, thereby improving motor function after SCI. However, the precise mechanisms by which sports training improves motor function after SCI remain incompletely understood. We established a rat model of T9 spinal cord contusion and initiated sports training 1 week after SCI, which continued for eight weeks. Using transcriptome sequencing validated through western blotting and immunostaining, we demonstrated that sports training effectively reduced neuroinflammation and prevented neuronal loss. Furthermore, we discovered that sports training changed neuronal microtubule dynamics, facilitating axon regeneration and synaptic plasticity and ultimately improving motor function. These findings indicate that the modulation of neuronal microtubule dynamics may represent a critical mechanism through which sports training improves motor function after SCI.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167587"},"PeriodicalIF":4.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression decreases immunity and PD-L1 inhibitor efficacy via the hypothalamic–pituitary–adrenal (HPA) axis in triple-negative breast cancer","authors":"Sheng Yu ,&nbsp;Chen Gan ,&nbsp;Wen Li ,&nbsp;Qianqian Zhang ,&nbsp;Yinlian Cai ,&nbsp;Jian Xu ,&nbsp;Runze Huang ,&nbsp;Senbang Yao ,&nbsp;Ling Cheng ,&nbsp;Huaidong Cheng","doi":"10.1016/j.bbadis.2024.167581","DOIUrl":"10.1016/j.bbadis.2024.167581","url":null,"abstract":"<div><h3>Background</h3><div>Depression weakens antitumor immunity, yet the underlying mechanisms linking depression and tumor growth remain unclear. This study examines the influence of depression on the hypothalamic–pituitary–adrenal (HPA) axis, immunological function, and effectiveness of immunotherapy in triple-negative breast cancer (TNBC) patients.</div></div><div><h3>Methods</h3><div>A mouse model of comorbid TNBC and depression was established via chronic restraint stress (CRS) and 4T1 tumor transplantation. A programmed cell death ligand 1 (PD-L1) inhibitor was used to manage mice with TNBC, and the ability of metyrapone to reverse the immune system changes induced by HPA axis activation in depression was evaluated. Mouse peripheral blood was used to measure HPA axis activity, immune cell numbers and cytokine levels.</div></div><div><h3>Results</h3><div>Depression activates the HPA axis, leading to increased levels of glucocorticoids. Depression led to an increase in the B-cell number and a reduction in the CD4⁺ T-cell and CD8⁺ T-cell numbers, without a statistically significant difference in the regulatory T (Treg) cell number. Furthermore, depression increased the levels of the cytokines interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α while decreasing the levels of IL-2 and IL-10. Similar results were observed in the context of PD-L1 inhibitor therapy. The depressed mice presented an increased tumor burden and a poor response to the PD-L1 inhibitor. The application of metyrapone during PD-L1 inhibitor treatment resulted in partial restoration of these depression-related alterations.</div></div><div><h3>Conclusions</h3><div>Depression reduces the effectiveness of PD-L1 inhibitors by altering the number of immune cells and the levels of cytokines through activation of the HPA axis.</div></div><div><h3>Translational relevance</h3><div>Depression is common in breast cancer patients and is associated with reduced antitumor immunity. There is limited knowledge regarding the specific mechanisms through which depression impairs antitumor immunity. Immunotherapy, which promotes the restoration of antitumor immunity, represents a promising treatment strategy for TNBC patients. However, the efficacy of immunotherapy can be compromised by depressive symptoms and the administration of glucocorticoids during treatment. It is still uncertain whether increasing glucocorticoid levels can reduce the efficacy of immunotherapy in patients with depression. The potential benefits of combining immunotherapy with glucocorticoid inhibitors compared with immunotherapy alone need to be evaluated for TNBC patients with concurrent depressive symptoms. Therefore, further clarification of the specific mechanisms by which depression impairs antitumor immunity is needed to inform future optimization of immunotherapy strategies.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167581"},"PeriodicalIF":4.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases","authors":"Martin W. Berchtold ,&nbsp;Antonio Villalobo","doi":"10.1016/j.bbadis.2024.167583","DOIUrl":"10.1016/j.bbadis.2024.167583","url":null,"abstract":"<div><div>Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca²⁺ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca²⁺/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca²⁺/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca²⁺/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167583"},"PeriodicalIF":4.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MMP8-mediated vascular remodeling in pulmonary hypertension","authors":"Xiaodong Deng ,&nbsp;Yong You ,&nbsp;Sheng Lv ,&nbsp;Yi Liu","doi":"10.1016/j.bbadis.2024.167582","DOIUrl":"10.1016/j.bbadis.2024.167582","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a vascular remodeling disease that impacts the cardiopulmonary system. Due to the currently limited understanding of vascular remodeling, a cure for PAH remains elusive. This study highlights the critical role of the STAT1 (signal transducer and activator of transcription 1)/MMP8 (matrix metallopeptidase 8)/DRP1 (dynamin-related protein 1) axis in vascular remodeling and the pathogenesis of pulmonary hypertension. Notably, MMP8 is significantly elevated in pulmonary arterial endothelial cells and its levels correlate with the severity of the disease. MMP8 binds to and activates DRP1, inducing mitochondrial fragmentation and promoting a malignant phenotype of endothelial cells under hypoxic conditions. Moreover, MMP8 is tightly regulated by STAT1. The knockout of MMP8 attenuates chronic pulmonary vascular remodeling, and drugs targeting MMP8 alleviate pulmonary hypertension and enhance cardiac function. This study offers fresh insights into hypoxia-induced vascular remodeling, laying a theoretical foundation for countering vascular remodeling by directly regulating the STAT1/MMP8/DRP1 axis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 2","pages":"Article 167582"},"PeriodicalIF":4.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}