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Current Opinion in Physiology最新文献

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Cardiac fibrosis in oncologic therapies 肿瘤治疗中的心脏纤维化
IF 2.5
Current Opinion in Physiology Pub Date : 2022-10-01 DOI: 10.1016/j.cophys.2022.100575
René R Sevag Packard
{"title":"Cardiac fibrosis in oncologic therapies","authors":"René R Sevag Packard","doi":"10.1016/j.cophys.2022.100575","DOIUrl":"10.1016/j.cophys.2022.100575","url":null,"abstract":"<div><p><span>Cardiotoxicity, or the development of unwarranted cardiovascular side-effects of oncologic therapies, can involve all aspects of cardiovascular disease. The development of cardiac fibrosis is a dreaded complication that leads to cardiac mechanical dysfunction, tachyarrhythmias, and an increase in </span>cardiovascular mortality<span>. This review details established and putative mechanisms, leading to fibroblast activation, myofibroblast<span> transdifferentiation, and the development of replacement or interstitial cardiac fibrosis as a consequence of cancer treatments. Clinical and imaging strategies for cardiac fibrosis assessment as well as emerging antifibrotic therapeutics will also be addressed.</span></span></p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"29 ","pages":"Article 100575"},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Mechanisms controlling selective elimination of damaged lysosomes 控制选择性消除受损溶酶体的机制
IF 2.5
Current Opinion in Physiology Pub Date : 2022-10-01 DOI: 10.1016/j.cophys.2022.100590
Melissa J Hoyer , Sharan Swarup , J Wade Harper
{"title":"Mechanisms controlling selective elimination of damaged lysosomes","authors":"Melissa J Hoyer ,&nbsp;Sharan Swarup ,&nbsp;J Wade Harper","doi":"10.1016/j.cophys.2022.100590","DOIUrl":"10.1016/j.cophys.2022.100590","url":null,"abstract":"<div><p>Lysosomes are subjected to physiological and pathophysiological insults over the course of their life cycle and are accordingly repaired or recycled. Lysophagy, the selective degradation of lysosomes via autophagy, occurs upon unrepairable lysosomal-membrane rupture; galectins bind to glycosylated macromolecules in the lysosome lumen, orchestrating a series of cellular responses to promote autophagic recycling of damaged lysosomes and transcriptional upregulation of lysosomal genes. Damaged lysosomes are ubiquitylated, resulting in the recruitment of ubiquitin-binding autophagy receptors, which promote assembly of an autophagosome around damaged lysosomes for delivery to healthy lysosomes for degradation. Here, we review the current state of our understanding of mechanisms used to mark and eliminate damaged lysosomes, and discuss the complexities of galectin function and ubiquitin-chain linkage types. Finally, we discuss the limitations of available data and challenges with the goal of understanding the mechanistic basis of key steps in lysophagic flux.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"29 ","pages":"Article 100590"},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878802/pdf/nihms-1865645.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Control of unconventional secretion by the autophagy machinery 自噬机制对非常规分泌的控制
IF 2.5
Current Opinion in Physiology Pub Date : 2022-10-01 DOI: 10.1016/j.cophys.2022.100595
Tan A Nguyen , Jayanta Debnath
{"title":"Control of unconventional secretion by the autophagy machinery","authors":"Tan A Nguyen ,&nbsp;Jayanta Debnath","doi":"10.1016/j.cophys.2022.100595","DOIUrl":"10.1016/j.cophys.2022.100595","url":null,"abstract":"<div><p><span>Autophagy is a highly conserved and critical recycling and degradation pathway that involves the selective engulfment of cytoplasmic organelles and proteins into double-membrane vesicles termed autophagosomes that subsequently fuse with </span>lysosomes<span> for degradation. In addition to its established role in protein degradation, there is a growing body of evidence that in response to specific environmental cues, the autophagy machinery promotes unconventional secretion of leaderless proteins via diverse mechanisms, collectively termed ‘secretory autophagy’. In this review, we describe recent findings highlighting these noncanonical functions of the autophagy machinery in specifying vesicular cargo loading for secretion and discuss how secretory autophagy is regulated during a wide range of cellular stresses, including inflammation, starvation, and lysosomal damage.</span></p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"29 ","pages":"Article 100595"},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75162608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Biochemical and structural imaging of remodeled myocardium 重构心肌的生化和结构成像
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100570
Choukri Mekkaoui , David E Sosnovik
{"title":"Biochemical and structural imaging of remodeled myocardium","authors":"Choukri Mekkaoui ,&nbsp;David E Sosnovik","doi":"10.1016/j.cophys.2022.100570","DOIUrl":"10.1016/j.cophys.2022.100570","url":null,"abstract":"<div><p>Remodeling of the myocardium results in changes in the molecular, cellular, and microstructural properties of the heart. Traditionally, these changes have been characterized using microscopy of tissue specimens taken from the heart. However, recent advances in biomedical imaging now make it possible to characterize many of these processes noninvasively. In this review, we focus on key principles and recent advances in molecular, cellular, and microstructural imaging of the heart after ischemic injury. Techniques to image cardiomyocyte death, inflammation, fibrosis, and microstructural remodeling of the heart are highlighted.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100570"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73443715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial function and dysfunction in innate immunity 线粒体功能与先天免疫功能障碍
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100571
Aurea Oliva , Carolina Meroño , Javier Traba
{"title":"Mitochondrial function and dysfunction in innate immunity","authors":"Aurea Oliva ,&nbsp;Carolina Meroño ,&nbsp;Javier Traba","doi":"10.1016/j.cophys.2022.100571","DOIUrl":"10.1016/j.cophys.2022.100571","url":null,"abstract":"<div><p>The mitochondria play an important role in the activation of the innate immune system. This organelle modulates the metabolic reprogramming of the immune cell into proinflammatory or anti-inflammatory subtypes, which typically utilize very different metabolic pathways to fulfill their functions. It also acts as a signaling platform to activate immune routes in both immune and nonimmune cells, as it can generate agonists for inflammatory pathways, including toll-like receptors, inflammasomes, or the cyclic GMP–AMP synthase–stimulator of interferon genes pathway, which lead to the generation of proinflammatory cytokines and antiviral molecules such as type-I interferons. These novel functions of the mitochondria are important in the fight against pathogens, but also contribute to human disease when dysregulated. This review describes recent findings in this field and highlights the role of mitochondrial nucleic acids in the regulation of innate immune signaling pathways.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100571"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S246886732200089X/pdfft?md5=cf921effbdcc67762a0cd063df89387a&pid=1-s2.0-S246886732200089X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78030959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
State of change: epigenetic and mitochondrial regulation of cardiac fibroblast activation 改变状态:心肌成纤维细胞活化的表观遗传和线粒体调控
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100557
Alexandra M Garvin , Taben M Hale
{"title":"State of change: epigenetic and mitochondrial regulation of cardiac fibroblast activation","authors":"Alexandra M Garvin ,&nbsp;Taben M Hale","doi":"10.1016/j.cophys.2022.100557","DOIUrl":"10.1016/j.cophys.2022.100557","url":null,"abstract":"<div><p><span>Cardiac fibroblasts (CFs) exist in a variety of states that contribute to either conserved or uncontrolled extracellular matrix (ECM) deposition. In healthy hearts, fibroblasts favor the homeostatic or quiescent state in which they work to maintain the ECM at a baseline level of activity. Acute or chronic injury in the form of myocardial infarction, hypertension, and heart failure induce CF activation via increased pro-oxidant, proinflammatory, and profibrotic stimuli secondary to hypoxia, cardiomyocyte cell death, or hemodynamic stress. In addition to the well-described signaling molecules that induce CF activation (e.g. </span>transforming growth factor beta 1, angiotensin II, and reactive oxygen species), there are emerging concepts that describe mechanisms that regulate more nuanced transition between activation states. This review will discuss recent descriptions of heterogeneous populations of resident cardiac fibroblasts, states of fibroblast activation, and the roles for mitochondrial and chromatin accessibility in mediating transition to and persistence of the activated state.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100557"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90103399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
IRE1/XBP1 and endoplasmic reticulum signaling — from basic to translational research for cardiovascular disease IRE1/XBP1和内质网信号——从心血管疾病的基础研究到转化研究
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100552
Fangyi Fu , Shirin Doroudgar
{"title":"IRE1/XBP1 and endoplasmic reticulum signaling — from basic to translational research for cardiovascular disease","authors":"Fangyi Fu ,&nbsp;Shirin Doroudgar","doi":"10.1016/j.cophys.2022.100552","DOIUrl":"10.1016/j.cophys.2022.100552","url":null,"abstract":"<div><p>Most cellular protein synthesis, including synthesis of membrane-targeted and secreted proteins, which are critical for cellular and organ crosstalk, takes place at the endoplasmic reticulum (ER), placing the ER at the nexus of cellular signaling, growth, metabolism, and stress sensing. Ample evidence has established the dysregulation of protein homeostasis and the ER unfolded protein response (UPR) in cardiovascular disease. However, the mechanisms of stress sensing and signaling in the ER are incompletely defined. Recent studies have defined notable functions for the inositol-requiring kinase 1 (IRE1)/X-box- binding protein-1 (XBP1) branch of the UPR in regulation of cardiac function. This review highlights the mechanisms underlying IRE1 activation and the IRE1 interactome, which reveals unexpected functions for the UPR and summarizes our current understanding of the functions of IRE1 in cardiovascular disease.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100552"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/2e/nihms-1884492.PMC10195104.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9551585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
m6A RNA methylation: a dynamic regulator of cardiac muscle and extracellular matrix m6A RNA甲基化:心肌和细胞外基质的动态调节因子
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100561
Charles P Rabolli , Federica Accornero
{"title":"m6A RNA methylation: a dynamic regulator of cardiac muscle and extracellular matrix","authors":"Charles P Rabolli ,&nbsp;Federica Accornero","doi":"10.1016/j.cophys.2022.100561","DOIUrl":"10.1016/j.cophys.2022.100561","url":null,"abstract":"<div><p><span>Post-transcriptional modifications encompass a large group of RNA<span><span> alterations that control gene expression. </span>Methylation of the N</span></span><sup>6</sup>-adenosine (m<sup>6</sup>A) of mRNA is a prevalent modification that alters the life cycle of transcripts. The roles that m<sup>6</sup><span>A play in regulating cardiac homeostasis and injury response are an active area of investigation, but it is clear that this chemical modification is a critical controller of fibroblast-to-myofibroblast transition, cardiomyocyte hypertrophy and division, and the structure and function of the extracellular matrix. Here, we discuss the latest findings of m</span><sup>6</sup>A in cardiac muscle and matrix.</p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100561"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Transcriptional regulation of cardiac fibroblast phenotypic plasticity 心脏成纤维细胞表型可塑性的转录调控
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100556
Kimberly N Burgos Villar , Xiaoyi Liu , Eric M Small
{"title":"Transcriptional regulation of cardiac fibroblast phenotypic plasticity","authors":"Kimberly N Burgos Villar ,&nbsp;Xiaoyi Liu ,&nbsp;Eric M Small","doi":"10.1016/j.cophys.2022.100556","DOIUrl":"10.1016/j.cophys.2022.100556","url":null,"abstract":"<div><p>Cardiac fibroblasts play critical roles in the maintenance of cardiac structure and the response to cardiac insult. Extracellular matrix deposition by activated resident cardiac fibroblasts, called myofibroblasts<span>, is an essential wound healing response. However, persistent fibroblast activation contributes to pathological fibrosis and cardiac chamber stiffening, which can cause diastolic dysfunction, heart failure, and initiate lethal arrhythmias. The dynamic and phenotypically plastic nature of cardiac fibroblasts is governed in part by the transcriptional regulation of genes encoding extracellular matrix molecules. Understanding how fibroblasts integrate various biomechanical cues into a precise transcriptional response may uncover therapeutic strategies to prevent fibrosis. Here, we provide an overview of the recent literature on transcriptional control of cardiac fibroblast plasticity and fibrosis, with a focus on canonical and noncanonical transforming growth factor beta<span> signaling, biomechanical regulation of Hippo/yes-associated protein and Rho/myocardin-related transcription factor signaling, and metabolic and epigenetic control of fibroblast activation.</span></span></p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100556"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Mechanics and matrix: positive feedback loops between fibroblasts and ECM drive interstitial cardiac fibrosis 机制和基质:成纤维细胞和ECM之间的正反馈循环驱动间质性心脏纤维化
IF 2.5
Current Opinion in Physiology Pub Date : 2022-08-01 DOI: 10.1016/j.cophys.2022.100560
Samuel J Coeyman , William J Richardson , Amy D Bradshaw
{"title":"Mechanics and matrix: positive feedback loops between fibroblasts and ECM drive interstitial cardiac fibrosis","authors":"Samuel J Coeyman ,&nbsp;William J Richardson ,&nbsp;Amy D Bradshaw","doi":"10.1016/j.cophys.2022.100560","DOIUrl":"10.1016/j.cophys.2022.100560","url":null,"abstract":"<div><p>Interstitial cardiac fibrosis arises due to deposition and accumulation of extracellular matrix (ECM) and occurs in hearts subject to increases in mechanical load. Cardiac fibroblasts sense changes in mechanical load through several mechanosensors including integrin ECM receptors and stretch activated ion channels<span>, which signal to induce ECM protein production through various pathways. Over time, processes intrinsic to fibroblasts and to the ECM occur to progress and sustain fibrosis through reciprocal, positive feedback loops. Changes in ECM include nascent collagen production, changes in ECM composition, and differential modification of collagen in fibers. Persistently fibrotic ECM contributes to a stiffer myocardium which can lead to the development of cardiomyopathies and heart failure.</span></p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"28 ","pages":"Article 100560"},"PeriodicalIF":2.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75652739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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