Journal of Cellular and Molecular Medicine最新文献_第6页

Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2 胰腺星状细胞源性外泌体tRF-19-PNR8YPJZ通过AXIN2促进胰腺癌的增殖和迁移

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-24 DOI: 10.1111/jcmm.17852

Wenpeng Cao, Shisi Dai, Wanyuan Ruan, Tingting Long, Zhirui Zeng, Shan Lei

{"title":"Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2","authors":"Wenpeng Cao, Shisi Dai, Wanyuan Ruan, Tingting Long, Zhirui Zeng, Shan Lei","doi":"10.1111/jcmm.17852","DOIUrl":"10.1111/jcmm.17852","url":null,"abstract":"The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2533-2546"},"PeriodicalIF":5.3,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation 白藜芦醇通过Sirt1/p53通路激活抑制脱铁性贫血并减缓心力衰竭进展。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-24 DOI: 10.1111/jcmm.17874

Wei Zhang, Shaohuan Qian, Bi Tang, Pinfang Kang, Heng Zhang, Chao Shi

{"title":"Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation","authors":"Wei Zhang, Shaohuan Qian, Bi Tang, Pinfang Kang, Heng Zhang, Chao Shi","doi":"10.1111/jcmm.17874","DOIUrl":"10.1111/jcmm.17874","url":null,"abstract":"Resveratrol is an organic compound widely studied for its therapeutic uses. We investigated whether resveratrol exerts cardioprotective effects by inhibiting ferroptosis via the Sirt1/p53 pathway. A heart failure model was established by aortic coarctation in Sirt1 knockout mice. The superoxide dismutase (SOD), glutathione (GSH) levels and mitochondrial morphology in murine heart tissues were assessed at different time points to determine the role of ferroptosis in heart failure progression. The cardiac function of mice with heart failure was evaluated by determining the brain natriuretic peptide (BNP) and sST2 concentration and conducting echocardiography. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were transfected with the p53 K382R mutant and Sirt1 interference lentiviral vectors. Immunoprecipitation (IP) experiments were performed to investigate whether Sirt1 influences ferroptosis via p53 K382 acetylation and SLC7A11 expression modulation. Resveratrol improved cardiac function in mice and decelerated ferroptosis and fibrosis progression in heart failure. However, the ability of resveratrol to prevent ferroptosis and treat heart failure was lost after silencing Sirt1. Sirt1 reduced ferroptosis by diminishing the levels of p53 K382 acetylation, reducing the degradation of SLC7A11, and increasing the levels of GSH and glutathione peroxidase 4 (GPX4) in cells. In conclusion, by activating the Sirt1/p53 pathway in heart failure, resveratrol decreased the depletion of SLC7A11, inhibited ferroptosis, and improved cardiac function.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3075-3089"},"PeriodicalIF":5.3,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

SNORA73B promotes endometrial cancer progression through targeting MIB1 and regulating host gene RCC1 alternative splicing SNORA73B通过靶向MIB1和调节宿主基因RCC1选择性剪接促进子宫内膜癌症进展。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-24 DOI: 10.1111/jcmm.17850

Xi Chen, Qian-hui Li, Bu-min Xie, Yu-meng Ji, Yang Han, Yang Zhao

{"title":"SNORA73B promotes endometrial cancer progression through targeting MIB1 and regulating host gene RCC1 alternative splicing","authors":"Xi Chen, Qian-hui Li, Bu-min Xie, Yu-meng Ji, Yang Han, Yang Zhao","doi":"10.1111/jcmm.17850","DOIUrl":"10.1111/jcmm.17850","url":null,"abstract":"Endometrial cancer (EC) is a common gynaecological malignant tumour with unclear pathogenesis. Small nucleolar RNA (snoRNA) is involved in many biological processes, including those of cancers. Using the Cancer Genome Atlas (TCGA) database, the expression pattern of a snoRNA, SNORA73B, was analysed. The biological functions of SNORA73B were assessed by in vitro proliferation, apoptosis, migration, and invasion assays and in vivo by the xenograft model. RNA sequencing (RNA-seq) and RNA immunoprecipitation assays were performed to determine the relationship between SNORA73B and its target genes. High-performance liquid chromatography (HPLC) was performed to detect the pseudouridine content of the mindbomb E3 ubiquitin protein ligase 1 gene (MIB1). The stability of MIB1 mRNA was evaluated using a transcription inhibitor, actinomycin D. By performing co-immunoprecipitation assays, the change in the ubiquitin levels of the Jagged canonical Notch ligand 1 (Jag 1), caused by SNORA73B and MIB1, was identified. RNA-seq and qRT-PCR were performed to detect the alternative splicing of the regulator of the chromosome condensation 1 gene (RCC1). The TCGA database analysis showed that SNORA73B was highly expressed in EC. SNORA73B promoted cell proliferation, migration, and invasion and inhibited apoptosis. SNORA73B modified the pseudouridine content in MIB1 and increased the stability of MIB1 mRNA and protein; thus, it affected Jag 1 ubiquitination and further activated the Notch pathway. SNORA73B also affected the alternative splicing of RCC1, increasing the number of transcripts, RCC1-T2 and RCC1-T3, which promoted cell proliferation, migration, and invasion. SNORA73B can be a potential target for EC.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2890-2905"},"PeriodicalIF":5.3,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A concise review on the role of MIR100HG in human disorders 综述MIR100HG在人类疾病中的作用

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-24 DOI: 10.1111/jcmm.17875

Soudeh Ghafouri-Fard, Atefeh Harsij, Hossein Farahzadi, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Mokhtari

引用次数: 0

Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase 原儿茶酸通过下调犬尿氨酸-3-单加氧酶预防异丙肾上腺素诱导的小鼠心力衰竭

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-22 DOI: 10.1111/jcmm.17869

Liyan Bai, Xiongyi Han, Hae Jin Kee, Xiaonan He, Seong Hoon Kim, Mi Jin Jeon, Hongyan Zhou, Seong Min Jeong, Seung-Jung Kee, Myung Ho Jeong

{"title":"Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase","authors":"Liyan Bai, Xiongyi Han, Hae Jin Kee, Xiaonan He, Seong Hoon Kim, Mi Jin Jeon, Hongyan Zhou, Seong Min Jeong, Seung-Jung Kee, Myung Ho Jeong","doi":"10.1111/jcmm.17869","DOIUrl":"10.1111/jcmm.17869","url":null,"abstract":"Protocatechuic acid (3,4-dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol-induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high-dose isoproterenol (80 mg/kg body weight) for 14 days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol-induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart-weight-to-body-weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine-3-monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short-interfering RNA against Kmo ameliorated transforming growth factor β1–induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. Kmo knockdown attenuated the isoproterenol-induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression–induced increases in Nppb mRNA levels. Protocatechuic acid or Kmo knockdown decreased isoproterenol-induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 16","pages":"2290-2307"},"PeriodicalIF":5.3,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10059395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MTHFD2 promotes PD-L1 expression via activation of the JAK/STAT signalling pathway in bladder cancer MTHFD2通过激活膀胱癌症中的JAK/STAT信号通路促进PD-L1表达。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-21 DOI: 10.1111/jcmm.17863

Linzhi Li, Yunlong Zhang, Weimin Hu, Fan Zou, Jinzhuo Ning, Ting Rao, Yuan Ruan, Weimin Yu, Fan Cheng

{"title":"MTHFD2 promotes PD-L1 expression via activation of the JAK/STAT signalling pathway in bladder cancer","authors":"Linzhi Li, Yunlong Zhang, Weimin Hu, Fan Zou, Jinzhuo Ning, Ting Rao, Yuan Ruan, Weimin Yu, Fan Cheng","doi":"10.1111/jcmm.17863","DOIUrl":"10.1111/jcmm.17863","url":null,"abstract":"Although combination chemotherapy is widely used for bladder cancer (BC) treatment, the recurrence and progression rates remain high. Therefore, novel therapeutic targets are required. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) contributes to tumourigenesis and immune evasion in several cancers; however, its biological function in BC remains unknown. This study aimed to investigate the expression, prognostic value and protumoural function of MTHFD2 in BC and elucidate the mechanism of programmed death-ligand 1 (PD-L1) upregulation by MTHFD2. An analysis using publicly available databases revealed that a high MTHFD2 expression was correlated with clinical features and a poor prognosis in BC. Furthermore, MTHFD2 promoted the growth, migration, invasion and tumourigenicity and decreased the apoptosis of BC cells in vivo and in vitro. The results obtained from databases showed that MTHFD2 expression was correlated with immune infiltration levels, PD-L1 expression, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. The expression of MTHFD2, PD-L1 and JAK/STAT signalling pathway-related proteins increased after interferon gamma treatment and decreased after MTHFD2 knockdown. Moreover, addition of a JAK/STAT pathway activator partially reduced the effect of MTHFD2 knockdown on BC cells. Collectively, our findings suggest that MTHFD2 promotes the expression of PD-L1 through the JAK/STAT signalling pathway in BC.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2922-2936"},"PeriodicalIF":5.3,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9854165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1 PKN1在胶质瘤发病中的作用及雷洛昔芬靶向PKN1的抗胶质瘤作用

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-21 DOI: 10.1111/jcmm.17860

Yubing Hao, Zelin Li, Anling Zhang, Li Sun, Guangxiu Wang, Hu Wang, Zhifan Jia

{"title":"The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1","authors":"Yubing Hao, Zelin Li, Anling Zhang, Li Sun, Guangxiu Wang, Hu Wang, Zhifan Jia","doi":"10.1111/jcmm.17860","DOIUrl":"10.1111/jcmm.17860","url":null,"abstract":"PKN1 (protein kinase N1), a serine/threonine protein kinase family member, is associated with various cancers. However, the role of PKN1 in gliomas has rarely been studied. We suggest that PKN1 expression in glioma specimens is considerably upregulated and positively correlates with the histopathological grading of gliomas. Knocking down PKN1 expression in glioblastoma (GBM) cells inhibits GBM cell proliferation, invasion and migration and promotes apoptosis. In addition, yes-associated protein (YAP) expression, an essential effector of the Hippo pathway contributing to the oncogenic role of gliomagenesis, was also downregulated. In contrast, PKN1 upregulation enhances the malignant characteristics of GBM cells and simultaneously upregulates YAP expression. Therefore, PKN1 is a promising therapeutic target for gliomas. Raloxifene (Ralo), a commonly used selective oestrogen-receptor modulator to treat osteoporosis in postmenopausal women, was predicted to target PKN1 according to the bioinformatics team from the School of Mathematics, Tianjin Nankai University. We showed that Ralo effectively targets PKN1, inhibits GBM cells proliferation and migration and sensitizes GBM cells to the major chemotherapeutic drug, Temozolomide. Ralo also reverses the effect of PKN1 on YAP activation. Thus, we confirm that PKN1 contributes to the pathogenesis of gliomas and may be a potential target for Ralo adjuvant glioma therapy.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2730-2743"},"PeriodicalIF":5.3,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway 对长链非编码RNA SNAI3-AS1的修正通过调节UPF1/Smad7信号通路促进肝癌的增殖和转移

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-21 DOI: 10.1111/jcmm.17769

引用次数: 0

Irreversible repolarization of tumour-associated macrophages by low-Pi stress inhibits the progression of hepatocellular carcinoma 低Pi应激下肿瘤相关巨噬细胞的不可逆复极抑制肝细胞癌的进展。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-20 DOI: 10.1111/jcmm.17861

Yang-feng Lv, Zi-qiang Liao, Qiu-chen Bi, Chuan-sheng Xie, Xiao-yong Wei, Yi Yun, Yuan-qiao He, Qun Tang

{"title":"Irreversible repolarization of tumour-associated macrophages by low-Pi stress inhibits the progression of hepatocellular carcinoma","authors":"Yang-feng Lv, Zi-qiang Liao, Qiu-chen Bi, Chuan-sheng Xie, Xiao-yong Wei, Yi Yun, Yuan-qiao He, Qun Tang","doi":"10.1111/jcmm.17861","DOIUrl":"10.1111/jcmm.17861","url":null,"abstract":"Numerous studies have shown the positive correlation between high levels of Pi and tumour progression. A critical goal of macrophage-based cancer therapeutics is to reduce anti-inflammatory macrophages (M2) and increase proinflammatory antitumour macrophages (M1). This study aimed to investigate the relationship between macrophage polarization and low-Pi stress. First, the spatial populations of M2 and M1 macrophages in 22 HCC patient specimens were quantified and correlated with the local Pi concentration. The levels of M2 and M1 macrophage markers expressed in the peritumour area were higher than the intratumour levels, and the expression of M2 markers was positively correlated with Pi concentration. Next, monocytes differentiated from THP-1 cells were polarized against different Pi concentrations to investigate the activation or silencing of the expression of p65, IκB-α and STAT3 as well as their phosphorylation. Results showed that low-Pi stress irreversibly repolarizes tumour-associated macrophages (TAMs) towards the M1 phenotype by silencing stat6 and activating p65. Moreover, HepG-2 and SMCC-7721 cells were cultured in conditioned medium to investigate the innate anticancer immune effects on tumour progression. Both cancer cell lines showed reduced proliferation, migration and invasion, as epithelial–mesenchymal transition (EMT) was inactivated. In vivo therapeutic effect on the innate and adaptive immune processes was validated in a subcutaneous liver cancer model by the intratumoural injection of sevelamer. Tumour growth was significantly inhibited by the partial deprivation of intratumoural Pi as the tumour microenvironment under low-Pi stress is more immunostimulatory. The anticancer immune response, activated by low-Pi stress, suggests a new macrophage-based immunotherapeutic modality.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2906-2921"},"PeriodicalIF":5.3,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of MiR-106b-5p mediated by exosomes mitigates acute kidney injury by modulating transmissible endoplasmic reticulum stress and M1 macrophage polarization 外泌体介导的对MiR-106b-5p的抑制通过调节可传递的内质网应激和M1巨噬细胞极化来减轻急性肾损伤。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-07-20 DOI: 10.1111/jcmm.17848

Xiang Li, Yanan Zhong, Rui Yue, Juan Xie, Yiyuan Zhang, Yongtao Lin, Hailun Li, Yong Xu, Donghui Zheng

{"title":"Inhibition of MiR-106b-5p mediated by exosomes mitigates acute kidney injury by modulating transmissible endoplasmic reticulum stress and M1 macrophage polarization","authors":"Xiang Li, Yanan Zhong, Rui Yue, Juan Xie, Yiyuan Zhang, Yongtao Lin, Hailun Li, Yong Xu, Donghui Zheng","doi":"10.1111/jcmm.17848","DOIUrl":"10.1111/jcmm.17848","url":null,"abstract":"Acute kidney injury (AKI), mainly caused by Ischemia/reperfusion injury (IRI), is a common and severe life-threatening disease with high mortality. Accumulating evidence suggested a direct relationship between endoplasmic reticulum (ER) stress response and AKI progression. However, the role of the transmissible ER stress response, a new modulator of cell-to-cell communication, in influencing intercellular communication between renal tubular epithelial cells (TECs) and macrophages in the AKI microenvironment remains to be determined. To address this issue, we first demonstrate that TECs undergoing ER stress are able to transmit ER stress to macrophages via exosomes, promoting macrophage polarization towards the pro-inflammatory M1 phenotype in vitro and in vivo. Besides, the miR-106b-5p/ATL3 signalling axis plays a pivotal role in the transmission of ER stress in the intercellular crosstalk between TECs and macrophages. We observed an apparent increase in the expression of miR-106b-5p in ER-stressed TECs. Furthermore, we confirmed that ALT3 is a potential target protein of miR-106b-5p. Notably, the inhibition of miR-106b-5p expression in macrophages not only restores ATL3 protein level but also decreases transmissible ER stress and hinders M1 polarization, thus alleviating AKI progression. Additionally, our results suggest that the level of exosomal miR-106b-5p in urine is closely correlated with the severity of AKI patients. Taken together, our study sheds new light on the crucial role of transmissible ER stress in the treatment of AKI through the regulation of the miR-106b-5p/ATL3 axis, offering new ideas for treating AKI.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2876-2889"},"PeriodicalIF":5.3,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0