Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104815
Ashton N. Jorgensen , Chowdhury S. Abdullah , Md. Shenuarin Bhuiyan , Megan Watt , Paari Dominic , Gopi K. Kolluru , Christopher G. Kevil , Hyung W. Nam
Intracellular Ca2+-calmodulin (CaM) signaling plays an important role in Ca2+-CaM-dependent kinase (CaMKII) and calcineurin (CaN)-mediated cardiac biology. While neurogranin (Ng) is known as a major Ca2+-CaM modulator in the brain, its pathophysiological role in cardiac hypertrophy has never been studied before. In the present study, we report that Ng is expressed in the heart and depletion of Ng dysregulates Ca2+ homeostasis and promotes cardiac failure in mice. 10-month-old Ng null mice demonstrate significantly increased heart-to-body weight ratios compared to wild-type. Using histological approaches, we identified that depletion of Ng increases cardiac hypertrophy, fibrosis, and collagen deposition near perivascular areas in the heart tissue of Ng null mice. Ca2+ spark experiments revealed that cardiac myocytes isolated from Ng null mice have decreased spark frequency and width, while the duration of sparks is significantly increased. We also identified that a lack of Ng increases CaMKIIδ signaling and periostin protein expression in these mouse hearts. Overall, we are the first study to explore how Ng expression in the heart plays an important role in Ca2+ homeostasis in cardiac myocytes as well as the pathophysiology of cardiac hypertrophy and fibrosis.
{"title":"Neurogranin regulates calcium-dependent cardiac hypertrophy","authors":"Ashton N. Jorgensen , Chowdhury S. Abdullah , Md. Shenuarin Bhuiyan , Megan Watt , Paari Dominic , Gopi K. Kolluru , Christopher G. Kevil , Hyung W. Nam","doi":"10.1016/j.yexmp.2022.104815","DOIUrl":"10.1016/j.yexmp.2022.104815","url":null,"abstract":"<div><p>Intracellular Ca<sup>2+</sup>-calmodulin (CaM) signaling plays an important role in Ca<sup>2+</sup><span><span>-CaM-dependent kinase (CaMKII) and calcineurin (CaN)-mediated cardiac biology. While </span>neurogranin (Ng) is known as a major Ca</span><sup>2+</sup><span>-CaM modulator in the brain, its pathophysiological role in cardiac hypertrophy has never been studied before. In the present study, we report that Ng is expressed in the heart and depletion of Ng dysregulates Ca</span><sup>2+</sup><span><span> homeostasis and promotes cardiac failure in mice. 10-month-old Ng </span>null mice demonstrate significantly increased heart-to-body weight ratios compared to wild-type. Using histological approaches, we identified that depletion of Ng increases cardiac hypertrophy, fibrosis, and collagen deposition near perivascular areas in the heart tissue of Ng null mice. Ca</span><sup>2+</sup><span> spark experiments revealed that cardiac myocytes isolated from Ng null mice have decreased spark frequency and width, while the duration of sparks is significantly increased. We also identified that a lack of Ng increases CaMKII</span><sub>δ</sub><span> signaling and periostin<span> protein expression in these mouse hearts. Overall, we are the first study to explore how Ng expression in the heart plays an important role in Ca</span></span><sup>2+</sup><span> homeostasis in cardiac myocytes as well as the pathophysiology of cardiac hypertrophy and fibrosis.</span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104815"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104785
Jinliang Li , Yuxi Qi
{"title":"Retraction notice to “Ginsenoside Rg3 inhibits cell growth, migration and invasion in Caco-2 cells by downregulation of lncRNA CCAT1” [Experimental and Molecular Pathology 106 (2019) 131–138]","authors":"Jinliang Li , Yuxi Qi","doi":"10.1016/j.yexmp.2022.104785","DOIUrl":"https://doi.org/10.1016/j.yexmp.2022.104785","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104785"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000454/pdfft?md5=fcb2763399b4c9d52f8b1d22cf7323f2&pid=1-s2.0-S0014480022000454-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71716578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104788
Chunhua Dai , Shanhao Jiang , Cuiying Chu , Meng Xin , Xiufen Song , Bojun Zhao
{"title":"Retraction notice to “ Baicalin protects human retinal pigment epithelial cell lines against high glucose-induced cell injury by up-regulation of microRNA-145” [Experimental and Molecular Pathology 106 (2019) 123–130]","authors":"Chunhua Dai , Shanhao Jiang , Cuiying Chu , Meng Xin , Xiufen Song , Bojun Zhao","doi":"10.1016/j.yexmp.2022.104788","DOIUrl":"10.1016/j.yexmp.2022.104788","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104788"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S001448002200048X/pdfft?md5=95e8c003d343800aeeb2f53b72a95df1&pid=1-s2.0-S001448002200048X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104800
Pengmu Xie, Xiuling Wang, Min Kong, Xiuyu Bai, Tao Jiang
{"title":"Retraction notice to \"TRAF4 promotes endometrial cancer cell growth and migration by activation of PI3K/AKT/Oct4 signaling\" [Experimental and Molecular Pathology 108 (2019) 9–16]","authors":"Pengmu Xie, Xiuling Wang, Min Kong, Xiuyu Bai, Tao Jiang","doi":"10.1016/j.yexmp.2022.104800","DOIUrl":"10.1016/j.yexmp.2022.104800","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104800"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000636/pdfft?md5=888ebbfce4f5aa335ba74c947fefa722&pid=1-s2.0-S0014480022000636-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104811
Rong Zhang , Bei Zhong , Jiashan He , Xinyu Yang , Menghua He , Wuyi Zeng , Jiayi Pan , Zixuan Fang , Jiangtao Jia , Hui Liu
Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain liver diseases. Resident hepatic macrophage-mediated inflammation influences the development of chronic liver diseases and cancer. Here, the first systematic study of macrophages heterogeneity in mice was conducted to illustrate the pathogenesis of MDB formation using single-nucleus RNA sequencing (snRNA-seq). Furthermore, we provided transcriptional profiles of macrophages obtained from the fractionation of mouse liver tissues following chronic injury. We equally identified seven discrete macrophage subpopulations, each involved in specific cellular activated pathways such as basal metabolism, immune regulation, angiogenesis, and cell cycle regulation. Among these, a specific macrophage cluster (Cluster4), a subpopulation specifically expressing genes that regulate cell division and the cell cycle, was identified. Interestingly, we found that CCR2 was significantly induced in Cluster2, thereby inducing monocytes to migrate to macrophages to promote MDB pathogenesis. Thus, our study is the first to demonstrate the heterogeneity of macrophages associated with liver MDB formation in mice through single-cell resolution. This serves as the basis for further insights into the pathogenesis of liver MDB formation and molecular mechanisms of chronic liver disease progression.
{"title":"Single-cell transcriptomes identifies characteristic features of mouse macrophages in liver Mallory-Denk bodies formation","authors":"Rong Zhang , Bei Zhong , Jiashan He , Xinyu Yang , Menghua He , Wuyi Zeng , Jiayi Pan , Zixuan Fang , Jiangtao Jia , Hui Liu","doi":"10.1016/j.yexmp.2022.104811","DOIUrl":"10.1016/j.yexmp.2022.104811","url":null,"abstract":"<div><p>Mallory-Denk bodies (MDBs) consist of intracellular aggregates of misfolded proteins in ballooned hepatocytes and serve as important markers of progression in certain liver diseases. Resident hepatic macrophage-mediated inflammation influences the development of chronic liver diseases and cancer. Here, the first systematic study of macrophages heterogeneity in mice was conducted to illustrate the pathogenesis of MDB formation using single-nucleus RNA sequencing (snRNA-seq). Furthermore, we provided transcriptional profiles of macrophages obtained from the fractionation of mouse liver tissues following chronic injury. We equally identified seven discrete macrophage subpopulations, each involved in specific cellular activated pathways such as basal metabolism, immune regulation, angiogenesis, and cell cycle regulation. Among these, a specific macrophage cluster (Cluster4), a subpopulation specifically expressing genes that regulate cell division and the cell cycle, was identified. Interestingly, we found that CCR2 was significantly induced in Cluster2, thereby inducing monocytes to migrate to macrophages to promote MDB pathogenesis. Thus, our study is the first to demonstrate the heterogeneity of macrophages associated with liver MDB formation in mice through single-cell resolution. This serves as the basis for further insights into the pathogenesis of liver MDB formation and molecular mechanisms of chronic liver disease progression.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104811"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000740/pdfft?md5=a81a1476df396eda5cf9981ab3b6069f&pid=1-s2.0-S0014480022000740-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40517168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104782
Zhongyan Mou , Yan Wang , Yongmei Li
{"title":"Retraction notice to “Brazilein induces apoptosis and G1/G0 phase cell cycle arrest by up-regulation of miR-133a in human vestibular schwannoma cells” [Experimental and Molecular Pathology 107 (2019) 95–101]","authors":"Zhongyan Mou , Yan Wang , Yongmei Li","doi":"10.1016/j.yexmp.2022.104782","DOIUrl":"10.1016/j.yexmp.2022.104782","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104782"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000429/pdfft?md5=77009bb3191f5152d4db407537860af0&pid=1-s2.0-S0014480022000429-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40460422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.yexmp.2022.104808
Yuxia Liu , Yan Zhang
{"title":"Retraction notice to “Lycium barbarum polysaccharides alleviate hydrogen peroxide-induced injury by up-regulation of miR-4295 in human trabecular meshwork cells” [Experimental and Molecular Pathology 106 (2019) 109–115]","authors":"Yuxia Liu , Yan Zhang","doi":"10.1016/j.yexmp.2022.104808","DOIUrl":"10.1016/j.yexmp.2022.104808","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"127 ","pages":"Article 104808"},"PeriodicalIF":3.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000715/pdfft?md5=a76d1c5023fc48a38107e5eb83597830&pid=1-s2.0-S0014480022000715-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40492676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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