Experimental cell research最新文献

{"title":"Changes and significance of Th1/Th2 and Treg/Th17 cells and their cytokines in patients with alopecia areata","authors":"Xiaojing Yang ,&nbsp;Wei Zhang ,&nbsp;Xuming Zhao ,&nbsp;Wenli Hou ,&nbsp;Yuanhui Wu ,&nbsp;Dongmei Feng ,&nbsp;Zhaoying Meng ,&nbsp;Xiangzhao Zhou","doi":"10.1016/j.yexcr.2024.114259","DOIUrl":"10.1016/j.yexcr.2024.114259","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA.</div></div><div><h3>Methods</h3><div>AA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared.</div></div><div><h3>Results</h3><div>AA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients.</div></div><div><h3>Conclusion</h3><div>Th1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114259"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the regulation of EGF signaling by miRNAs, delving into the underlying mechanism and signaling pathways in cancer","authors":"Darmadi Darmadi ,&nbsp;Zafar Aminov ,&nbsp;Ahmed Hjazi ,&nbsp;Roopashree R ,&nbsp;Syeda Wajida Kazmi ,&nbsp;Yasser Fakri Mustafa ,&nbsp;Beneen Hosseen ,&nbsp;Abhishek Sharma ,&nbsp;Mahmood Hasen Shuhata Alubiady ,&nbsp;Salah Hassan Zain Al-Abdeen","doi":"10.1016/j.yexcr.2024.114267","DOIUrl":"10.1016/j.yexcr.2024.114267","url":null,"abstract":"<div><div>The EGF receptors (EGFRs) signaling pathway is essential for tumorigenesis and progression of cancer. Emerging evidence suggests that miRNAs are essential regulators of EGF signaling, influencing various pathway components and tumor behavior. This article discusses the underlying mechanisms and clinical implications of miRNA-mediated regulation of EGF signaling in cancer. miRNAs utilize multiple mechanisms to exert their regulatory effects on EGF signaling. They can target EGF ligands, including EGF and TGF-directly, inhibiting their expression and secretion. In addition, miRNAs can modulate EGF signaling indirectly by targeting EGF receptors, downstream signaling molecules, and transcription factors implicated in regulating the EGF pathway. These miRNAs can disrupt the delicate equilibrium of EGF signaling, resulting in aberrant activation and fostering tumor cell proliferation, survival, angiogenesis, and metastasis. The dysregulation of the expression of specific miRNAs has been linked to clinical outcomes in numerous types of cancer. Specific profiles of miRNA expression have been identified as prognostic markers, reflecting tumor characteristics, invasiveness, metastatic potential, and therapeutic response. These miRNAs can serve as potential therapeutic targets for interventions that modulate EGF signaling and improve patient outcomes. Understanding the intricate relationship between miRNAs and EGF signaling in cancer can transform cancer diagnosis, prognosis, and treatment. The identification of specific miRNAs involved in the regulation of the EGF pathway opens the door to the development of targeted therapies and personalized medicine approaches. In addition, miRNA-based interventions promise to overcome therapeutic resistance and improve the efficacy of existing treatments. miRNAs are crucial regulators of EGF signaling in cancer, affecting tumor behavior and clinical outcomes. Further research is required to decipher the complex network of miRNA-mediated EGF signaling regulation and translate these findings into clinically applicable strategies for enhanced cancer treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114267"},"PeriodicalIF":3.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess glucose alone induces hepatocyte damage due to oxidative stress and endoplasmic reticulum stress","authors":"Tsuguru Hayashi,&nbsp;Shinji Oe,&nbsp;Koichiro Miyagawa,&nbsp;Masashi Kusanaga,&nbsp;Noriyoshi Ogino,&nbsp;Yuichi Honma,&nbsp;Masaru Harada","doi":"10.1016/j.yexcr.2024.114264","DOIUrl":"10.1016/j.yexcr.2024.114264","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (DM) is a significant risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). With the increasing prevalence of type 2 DM and MASLD due to lifestyle changes, understanding their impact on liver health is crucial. However, the hepatocellular damage caused by glucose alone is unknown. This study investigates the effect of excess glucose on hepatocytes, focusing on oxidative stress, endoplasmic reticulum stress (ER stress), apoptosis, autophagy, and cell proliferation. We treated an immortalized-human hepatocyte cell line with excess glucose and analyzed. Excess glucose induced oxidative stress and ER stress in a time- and concentration-dependent manner, leading to apoptosis. Oxidative stress and ER stress were independently induced by excess glucose. Proteasome inhibitors and palmitic acid exacerbated glucose-induced stress, leading to the formation of Mallory-Denk body-like inclusion bodies. Despite these stresses, autophagic flux was not altered. Excess glucose also caused DNA damage but did not affect cell proliferation. This suggests that glucose itself can contribute to the progression of metabolic dysfunction-associated steatohepatitis (MASH) and carcinogenesis of HCC in patients with type 2 DM. Managing blood glucose levels is crucial to prevent hepatocyte damage and associated complications.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114264"},"PeriodicalIF":3.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel molecular target, superoxide dismutase 1, in ALK inhibitor-resistant lung cancer cells, detected through proteomic analysis","authors":"Noriko Miyake ,&nbsp;Nobuaki Ochi ,&nbsp;Masami Takeyama ,&nbsp;Hideko Isozaki ,&nbsp;Eiki Ichihara ,&nbsp;Hiromichi Yamane ,&nbsp;Takuya Fukazawa ,&nbsp;Yasunari Nagasaki ,&nbsp;Tatsuyuki Kawahara ,&nbsp;Hidekazu Nakanishi ,&nbsp;Akio Hiraki ,&nbsp;Katsuyuki Kiura ,&nbsp;Nagio Takigawa","doi":"10.1016/j.yexcr.2024.114266","DOIUrl":"10.1016/j.yexcr.2024.114266","url":null,"abstract":"<div><h3>Backgrounds</h3><div>To the best of our knowledge, there are no reports of proteomic analysis for the identification of unknown proteins involved in resistance to anaplastic lymphoma kinase (ALK) inhibitors. In this study, we investigated the proteins involved in resistance to alectinib, a representative ALK inhibitor, through proteomic analysis and the possibility of overcoming resistance.</div></div><div><h3>Methods</h3><div>An ALK-positive lung adenocarcinoma cell line (ABC-11) and the corresponding alectinib-resistant cell line (ABC-11/CHR2) were used. Two-dimensional difference gel electrophoresis (2D DIGE) was performed; the stained gel was scanned and the spots were analyzed using DeCyder TM2D 7.0. Mass spectrometry (MS) with the UltrafleXtreme matrix-assisted laser desorption ionization-tandem time-of-flight (MALDI-TOF/TOF) MS system was performed. For the MS/MS analysis, the samples were spotted on an AnchorChipTM 600 TF plate. The peptide masses obtained in the reflector positive mode were acquired at <em>m</em>/<em>z</em> of 400−6000. MS/MS data were searched against the NCBI protein databases. Growth inhibition was measured using an MTT assay. The isobologram and combination index were calculated based on the median-effect analysis. Western blotting was performed using antibodies, including superoxide dismutase (SOD) 1, MET, ERK, PARP, AKT, and BRCA1.</div></div><div><h3>Results</h3><div>The 2D DIGE for ABC-11 and ABC-11/CHR2 showed different expression levels in about 2000 spots. SOD was identified from spots highly expressed in resistant strains. Western blotting also confirmed SOD1 overexpression in ABC-11/CHR2. siSOD1 enhanced the growth inhibitory effects of alectinib, increased cleaved PARP levels, and decreased pERK, pAKT, and BRCA1 levels with a combination of alectinib. In addition, the combination of LCS-1, an SOD1 inhibitor, and alectinib synergistically suppressed the growth in ABC-11/CHR2, but not in ABC-11.</div></div><div><h3>Conclusions</h3><div>SOD1 overexpression is thought to be a mechanism for alectinib resistance, suggesting the possibility of overcoming resistance using SOD1 inhibitors.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114266"},"PeriodicalIF":3.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of mesenchymal stem cells from different origins on the therapeutic effectiveness of systemic lupus erythematosus","authors":"Yuan Yuan,&nbsp;Tong Liu","doi":"10.1016/j.yexcr.2024.114263","DOIUrl":"10.1016/j.yexcr.2024.114263","url":null,"abstract":"<div><div>Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disorder characterized by alterations in the balance between inflammatory and regulatory cytokines. Mesenchymal stem cells (MSCs), which are non-hematopoietic stem cells with multipotent differentiation potential, due to their immunomodulatory, tissue repair, low immunogenicity, and chemotactic properties, have garnered increasing interest in SLE treatment. Studies increasingly reveal the heterogeneous nature of MSC populations. With sources including dental pulp, adipose tissue, bone marrow, and umbilical cord, the therapeutic effects of MSCs on SLE vary depending on their origin. This review consolidates clinical research on MSCs from different sources in treating SLE and analyzes the possible causes underlying these variable outcomes. Additionally, it elucidates five potential factors impacting the outcomes of MSC therapy in SLE: the influence of the microenvironment on MSCs, the complexity and paradoxical aspects of MSC mechanisms in SLE treatment, the heterogeneity of MSCs, the <em>in vivo</em> differentiation potential and post-transplant survival rates of MSCs, and disparities in MSC preparation conditions.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114263"},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A methyltransferase ZC3H13 improves pulmonary fibrosis in mice through regulating Bax expression","authors":"Jing Guan ,&nbsp;Lengyun Yin ,&nbsp;Qi Huang ,&nbsp;Jiamei Chen ,&nbsp;Hui Liu ,&nbsp;Jianmin Li","doi":"10.1016/j.yexcr.2024.114255","DOIUrl":"10.1016/j.yexcr.2024.114255","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease. N6-methyladenosine (m⁶A) is a reversible RNA modification that was shown to be associated with IPF development. The present study aimed to explore the function and potential mechanism of the m⁶A methylation enzyme zinc finger CCCH-type containing 13 (ZC3H13) in IPF. In the study, bioinformatic screening yielded a differentially expressed m⁶A gene, ZC3H13, which was down-regulated in GEO microarrays, BLM-induced mouse models, and cellular models. Overexpression of ZC3H13 reduced histopathological damage of lung tissues in mice, mitigated fibrosis (including reduced α-SMA, collagen Ⅰ, and Vimentin levels, and elevated E-cadherin levels), decreased lung/body weight ratio and lung hydroxyproline levels, reduced oxidative stress (increased SOD activity and GSH-Px activity and decreased MDA levels), suppressed apoptosis within lung tissues and MLE-12 cells, promoted Bcl-2 expression, and inhibited Bax expression. Bax expression was found to be negatively correlated with ZC3H13 expression by correlation analysis. ZC3H13 could bind Bax mRNA and promote its m⁶A methylation through reading protein YTHDC1, thereby inhibiting its stability. Bax inhibition ameliorated BLM-induced MLE-12 cell dysfunction and partially abrogated the inhibition of MLE-12 cell function by ZC3H13 downregulation. In conclusion, m⁶A methyltransferase ZC3H13 impedes lung epithelial cell apoptosis and thus improves pulmonary fibrosis by promoting Bax mRNA m⁶A methylation and down-regulating Bax expression through reading protein YTHDC1.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114255"},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Architecture of CTPS filament networks revealed by cryo-electron tomography","authors":"You Fu ,&nbsp;Chen-Jun Guo ,&nbsp;Zhi-Jie Liu ,&nbsp;Ji-Long Liu","doi":"10.1016/j.yexcr.2024.114262","DOIUrl":"10.1016/j.yexcr.2024.114262","url":null,"abstract":"<div><div>The cytoophidium is a novel type of membraneless organelle, first observed in the ovaries of <em>Drosophila</em> using fluorescence microscopy. <em>In vitro</em>, purified <em>Drosophila melanogaster</em> CTPS (dmCTPS) can form metabolic filaments under the presence of either substrates or products, and their structures that have been analyzed using cryo-electron microscopy (cryo-EM). These dmCTPS filaments are considered the fundamental units of cytoophidia. However, due to the resolution gap between light and electron microscopy, the precise assembly pattern of cytoophidia remains unclear. In this study, we find that dmCTPS filaments can spontaneously assemble <em>in vitro</em>, forming network structures that reach micron-scale dimensions. Using cryo-electron tomography (cryo-ET), we reconstruct the network structures formed by dmCTPS filaments under substrate or product binding conditions and elucidate their assembly process. The dmCTPS filaments initially form structural bundles, which then further assemble into larger networks. By identifying, tracking, and statistically analyzing the filaments, we observed distinct characteristics of the structural bundles formed under different conditions. This study provides the first systematic analysis of dmCTPS filament networks, offering new insights into the relationship between cytoophidia and metabolic filaments.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114262"},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014482724003537/pdfft?md5=24f45cf814818b4c23776844d32d213c&pid=1-s2.0-S0014482724003537-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NONRATT000538.2 promotes vascular smooth muscle cell phenotypic switch and in-stent restenosis","authors":"Jie Zhao,&nbsp;Yi Cheng,&nbsp;Min Zhou","doi":"10.1016/j.yexcr.2024.114260","DOIUrl":"10.1016/j.yexcr.2024.114260","url":null,"abstract":"<div><div>Vascular smooth muscle cell (VSMC) excessive proliferation and migration are considered the main pathological process in in-stent restenosis (ISR) following vascular intervention. Certain long noncoding RNAs play vital roles in this process. Therefore, this study aimed to explore novel regulators for ISR and further uncover the mechanism. Using a rat abdominal aorta stent implantation model, we observed that NONRATT000538.2 (NR538.2) served as a positive regulator for VSMC proliferation and migration. By manipulating NR538.2 expression via adenoviral overexpression or siRNA knockdown, we noted that NR538.2 promoted VSMC phenotypic switching, thereby inducing proliferation and migration. Significantly, the local delivery of siRNA of NR538.2 via adeno-associated virus vector suppressed balloon injury-induced neointima formation. Our study demonstrated for the first time that NR538.2 positively influenced VSMC proliferation during ISR.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114260"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The reduction of imidazole propionate induced by intermittent fasting promotes recovery of peripheral nerve injury by enhancing migration of Schwann cells","authors":"Weilong Tang ,&nbsp;Xiaoyu Yin ,&nbsp;Kunyu Liu ,&nbsp;Tuo Shao ,&nbsp;Qichang Gao ,&nbsp;Hongtao Shen ,&nbsp;Xin Zhong ,&nbsp;Zhenyu Zhang","doi":"10.1016/j.yexcr.2024.114261","DOIUrl":"10.1016/j.yexcr.2024.114261","url":null,"abstract":"<div><p>Peripheral nerve injury (PNI) accompanied with sensory and motor dysfunction has serious effect on the quality of life of patients. Intermittent fasting (IF), as a dietary pattern, has rarely been reported to influence imidazole propionate (ImP), a microbial metabolite, in vivo. To date, the link between ImP and PNI is unknown. This study aimed to explore the impact of ImP on the recovery after PNI and determine whether IF could reduce the concentration of ImP in vivo. Sciatic nerve injury rat model and RSC96 cells were utilized with 16s RNA seq, HE staining, CCK-8 assay, Western blot (WB), Transmission electron microscopy (TEM), immunofluorescence, transwell and scratch wound healing assays as read outs. WB, TEM, transwell and wound healing assay showed an inhibitory effect of ImP on autophagy and migration of Schwann cells. This negative effect on migration was reversed by rapamycin. Detection of p-Erk and p-mTOR confirmed that the MAPK/Erk/mTOR pathway was involved in this process. In vivo, IF changed the composition of gut microbiome, including bacteria related to ImP production and reduced the concentration of ImP in serum. In sum, IF influenced the composition of gut microbiome and reduced the concentration of ImP in vivo. The reduction of ImP promoted migration of SCs through enhancing autophagy which involved MAPK/Erk/mTOR pathway.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114261"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-derived exosomes attenuates pulmonary hypertension via inhibiting pulmonary vascular remodeling","authors":"Shanshan Zhang ,&nbsp;Junfu Wang ,&nbsp;Jiang Wen ,&nbsp;Qian Xin ,&nbsp;Jue Wang ,&nbsp;Zhiye Ju ,&nbsp;Yun Luan","doi":"10.1016/j.yexcr.2024.114256","DOIUrl":"10.1016/j.yexcr.2024.114256","url":null,"abstract":"<div><h3>Background</h3><p>Pulmonary hypertension (PH) is a serious cardiopulmonary disease with significant morbidity and mortality. Vascular obstruction leads to a continuous increase in pulmonary vascular resistance, vascular remodeling, and right ventricular hypertrophy and failure, which are the main pathological features of PH. Currently, the treatments for PH are very limited, so new methods are urgently needed. Msenchymal stem cells-derived exosomes have been shown to have significant therapeutic effects in PH, however, the mechanism still very blurry. Here, we investigated the possible mechanism by which umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-EXO) inhibited monocrotaline (MCT)-induced pulmonary vascular remodeling in a rat model of PH by regulating the NF-κB/BMP signaling pathway. Our data revealed that hUC-MSC-EXO could significantly attenuate MCT-induced PH and right ventricular hypertrophy. Moreover, the protein expression level of BMPR2, BMP-4, BMP-9 and ID1 was significantly increased, but NF-κB p65, p-NF-κB-p65 and BMP antagonists Gremlin-1 was increased in vitro and vivo. Collectively, this study revealed that the mechanism of hUC-MSC-EXO attenuates pulmonary hypertension may be related to inhibition of NF-κB signaling to further activation of BMP signaling. The present study provided a promising therapeutic strategy for PH vascular remodeling.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114256"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014482724003471/pdfft?md5=75d7fb244db13cf6bb8e658804cc5d46&pid=1-s2.0-S0014482724003471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}