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Annual review of physiology最新文献

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The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe? GDF15-GFRAL通路在健康和代谢疾病中的作用:是敌是友?
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-11-23 DOI: 10.1146/annurev-physiol-022020-045449
Samuel N Breit, David A Brown, Vicky Wang-Wei Tsai
{"title":"The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe?","authors":"Samuel N Breit,&nbsp;David A Brown,&nbsp;Vicky Wang-Wei Tsai","doi":"10.1146/annurev-physiol-022020-045449","DOIUrl":"https://doi.org/10.1146/annurev-physiol-022020-045449","url":null,"abstract":"<p><p>GDF15 is a cell activation and stress response cytokine of the glial cell line-derived neurotrophic factor family within the TGF-β superfamily. It acts through a recently identified orphan member of the GFRα family called GFRAL and signals through the Ret coreceptor. Cell stress and disease lead to elevated GDF15 serum levels, causing anorexia, weight loss, and alterations to metabolism, largely by actions on regions of the hindbrain. These changes restore homeostasis and, in the case of obesity, cause a reduction in adiposity. In some diseases, such as advanced cancer, serum GDF15 levels can rise by as much as 10-100-fold, leading to an anorexia-cachexia syndrome, which is often fatal. This review discusses how GDF15 regulates appetite and metabolism, the role it plays in resistance to obesity, and how this impacts diseases such as diabetes, nonalcoholic fatty liver disease, and anorexia-cachexia syndrome. It also discusses potential therapeutic applications of targeting the GDF15-GFRAL pathway and lastly suggests some potential unifying hypotheses for its biological role.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-022020-045449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38737631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 71
Renal Denervation to Treat Heart Failure. 肾去神经治疗心力衰竭。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-10-19 DOI: 10.1146/annurev-physiol-031620-093431
Thomas E Sharp, David J Lefer
{"title":"Renal Denervation to Treat Heart Failure.","authors":"Thomas E Sharp,&nbsp;David J Lefer","doi":"10.1146/annurev-physiol-031620-093431","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031620-093431","url":null,"abstract":"<p><p>Heart failure (HF) is a global pandemic with a poor prognosis after hospitalization. Despite HF syndrome complexities, evidence of significant sympathetic overactivity in the manifestation and progression of HF is universally accepted. Confirmation of this dogma is observed in guideline-directed use of neurohormonal pharmacotherapies as a standard of care in HF. Despite reductions in morbidity and mortality, a growing patient population is resistant to these medications, while off-target side effects lead to dismal patient adherence to lifelong drug regimens. Novel therapeutic strategies, devoid of these limitations, are necessary to attenuate the progression of HF pathophysiology while continuing to reduce morbidity and mortality. Renal denervation is an endovascular procedure, whereby the ablation of renal nerves results in reduced renal afferent and efferent sympathetic nerve activity in the kidney and globally. In this review, we discuss the current state of preclinical and clinical research related to renal sympathetic denervation to treat HF.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031620-093431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38509862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 23
Epigenetic Signatures and Plasticity of Intestinal and Other Stem Cells. 肠和其他干细胞的表观遗传特征和可塑性。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 DOI: 10.1146/annurev-physiol-021119-034520
Madhurima Saxena, Ramesh A Shivdasani
{"title":"Epigenetic Signatures and Plasticity of Intestinal and Other Stem Cells.","authors":"Madhurima Saxena,&nbsp;Ramesh A Shivdasani","doi":"10.1146/annurev-physiol-021119-034520","DOIUrl":"https://doi.org/10.1146/annurev-physiol-021119-034520","url":null,"abstract":"<p><p>The cardinal properties of adult tissue stem cells are self-renewal and the ability to generate diverse resident cell types. The daily losses of terminally differentiated intestinal, skin, and blood cells require \"professional\" stem cells to produce replacements. This occurs by continuous expansion of stem cells and their immediate progeny, followed by coordinated activation of divergent transcriptional programs to generate stable cells with diverse functions. Other tissues turn over slowly, if at all, and vary widely in strategies for facultative stem cell activity or interconversion among mature resident cell types (transdifferentiation). Cell fate potential is programmed in tissue-specific configurations of chromatin, which restrict the complement of available genes and <i>cis-</i>regulatory elements, hence allowing specific cell types to arise. Using as a model the transcriptional and chromatin basis of cell differentiation and dedifferentiation in intestinal crypts, we discuss here how self-renewing and other tissues execute homeostatic and injury-responsive stem cell activity.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-021119-034520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9560834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Metabolism in Pulmonary Hypertension. 肺动脉高压的代谢。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 DOI: 10.1146/annurev-physiol-031620-123956
Weiling Xu, Allison J Janocha, Serpil C Erzurum
{"title":"Metabolism in Pulmonary Hypertension.","authors":"Weiling Xu,&nbsp;Allison J Janocha,&nbsp;Serpil C Erzurum","doi":"10.1146/annurev-physiol-031620-123956","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031620-123956","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is characterized by impaired regulation of pulmonary hemodynamics and vascular growth. Alterations of metabolism and bioenergetics are increasingly recognized as universal hallmarks of PAH, as metabolic abnormalities are identified in lungs and hearts of patients, animal models of the disease, and cells derived from lungs of patients. Mitochondria are the primary organelle critically mediating the complex and integrative metabolic pathways in bioenergetics, biosynthetic pathways, and cell signaling. Here, we review the alterations in metabolic pathways that are linked to the pathologic vascular phenotype of PAH, including abnormalities in glycolysis and glucose oxidation, fatty acid oxidation, glutaminolysis, arginine metabolism, one-carbon metabolism, the reducing and oxidizing cell environment, and the tricarboxylic acid cycle, as well as the effects of PAH-associated nuclear and mitochondrial mutations on metabolism. Understanding of the metabolic mechanisms underlying PAH provides important knowledge for the design of new therapeutics for treatment of patients.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597719/pdf/nihms-1749316.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25356240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 54
Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration. 上皮干细胞和祖细胞在肺修复和再生中的作用。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-10-19 DOI: 10.1146/annurev-physiol-041520-092904
Konstantinos-Dionysios Alysandratos, Michael J Herriges, Darrell N Kotton
{"title":"Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration.","authors":"Konstantinos-Dionysios Alysandratos,&nbsp;Michael J Herriges,&nbsp;Darrell N Kotton","doi":"10.1146/annurev-physiol-041520-092904","DOIUrl":"https://doi.org/10.1146/annurev-physiol-041520-092904","url":null,"abstract":"<p><p>The mammalian lung epithelium is composed of a wide array of specialized cells that have adapted to survive environmental exposure and perform the tasks necessary for respiration. Although the majority of these cells are remarkably quiescent during adult lung homeostasis, a growing body of literature has demonstrated the capacity of these epithelial lineages to proliferate in response to injury and regenerate lost or damaged cells. In this review, we focus on the regionally distinct lung epithelial cell types that contribute to repair after injury, and we address current controversies regarding whether elite stem cells or frequent facultative progenitors are the predominant participants. We also shed light on the newly emerging approaches for exogenously generating similar lung epithelial lineages from pluripotent stem cells.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-041520-092904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38509864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 29
Olfactory Circuitry and Behavioral Decisions. 嗅觉回路和行为决定。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-11-23 DOI: 10.1146/annurev-physiol-031820-092824
Kensaku Mori, Hitoshi Sakano
{"title":"Olfactory Circuitry and Behavioral Decisions.","authors":"Kensaku Mori,&nbsp;Hitoshi Sakano","doi":"10.1146/annurev-physiol-031820-092824","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031820-092824","url":null,"abstract":"<p><p>In mammals, odor information detected by olfactory sensory neurons is converted to a topographic map of activated glomeruli in the olfactory bulb. Mitral cells and tufted cells transmit signals sequentially to the olfactory cortex for behavioral outputs. To elicit innate behavioral responses, odor signals are directly transmitted by distinct subsets of mitral cells from particular functional domains in the olfactory bulb to specific amygdala nuclei. As for the learned decisions, input signals are conveyed by tufted cells as well as by mitral cells to the olfactory cortex. Behavioral scene cells link the odor information to the valence cells in the amygdala to elicit memory-based behavioral responses. Olfactory decision and perception take place in relation to the respiratory cycle. How is the sensory quality imposed on the olfactory inputs for behavioral outputs? How are the two types of odor signals, innate and learned, processed during respiration? Here, we review recent progress on the study of neural circuits involved in decision making in the mouse olfactory system.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031820-092824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38737630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. SGLT2抑制剂对肾脏和心血管功能的影响。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 DOI: 10.1146/annurev-physiol-031620-095920
Volker Vallon, Subodh Verma
{"title":"Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function.","authors":"Volker Vallon,&nbsp;Subodh Verma","doi":"10.1146/annurev-physiol-031620-095920","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031620-095920","url":null,"abstract":"<p><p>SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose-dependent and -independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031620-095920","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10292438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 136
Sestrins in Physiological Stress Responses. 生理应激反应中的Sestrins
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-10-28 DOI: 10.1146/annurev-physiol-031620-092317
Myungjin Kim, Allison H Kowalsky, Jun Hee Lee
{"title":"Sestrins in Physiological Stress Responses.","authors":"Myungjin Kim,&nbsp;Allison H Kowalsky,&nbsp;Jun Hee Lee","doi":"10.1146/annurev-physiol-031620-092317","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031620-092317","url":null,"abstract":"<p><p>Sestrins are a family of proteins that respond to a variety of environmental stresses, including genotoxic, oxidative, and nutritional stresses. Sestrins affect multiple signaling pathways: AMP-activated protein kinase, mammalian target of rapamycin complexes, insulin-AKT, and redox signaling pathways. By regulating these pathways, Sestrins are thought to help adapt to stressful environments and subsequently restore cell and tissue homeostasis. In this review, we describe how Sestrins mediate physiological stress responses in the context of nutritional and chemical stresses (liver), physical movement and exercise (skeletal muscle), and chemical, physical, and inflammatory injuries (heart). These findings also support the idea that Sestrins are a molecular mediator of hormesis, a paradoxical beneficial effect of low- or moderate-level stresses in living organisms.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031620-092317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38535950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 19
Regulation of Hemogenic Endothelial Cell Development and Function. 造血内皮细胞发育和功能的调控。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 Epub Date: 2020-10-09 DOI: 10.1146/annurev-physiol-021119-034352
Yinyu Wu, Karen K Hirschi
{"title":"Regulation of Hemogenic Endothelial Cell Development and Function.","authors":"Yinyu Wu,&nbsp;Karen K Hirschi","doi":"10.1146/annurev-physiol-021119-034352","DOIUrl":"https://doi.org/10.1146/annurev-physiol-021119-034352","url":null,"abstract":"<p><p>Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) essential for establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells to become blood-forming, or hemogenic, and the subsequent endothelial-to-hematopoietic transition to generate HSPCs therefrom. The mechanisms that regulate these processes are under intensive investigation, as their recapitulation in vitro from human pluripotent stem cells has the potential to generate autologous HSPCs for clinical applications. In this review, we provide an overview of hemogenic endothelial cell development and highlight the molecular events that govern hemogenic specification of vascular endothelial cells and the generation of multilineage HSPCs from hemogenic endothelium. We also discuss the impact of hemogenic endothelial cell development on adult hematopoiesis.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-021119-034352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38473880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 24
Regulation of Mitochondrial Ca2+ Uptake. 线粒体Ca2+摄取的调控。
IF 18.2 1区 医学
Annual review of physiology Pub Date : 2021-02-10 DOI: 10.1146/annurev-physiol-031920-092419
Elizabeth Murphy, Charles Steenbergen
{"title":"Regulation of Mitochondrial Ca<sup>2+</sup> Uptake.","authors":"Elizabeth Murphy,&nbsp;Charles Steenbergen","doi":"10.1146/annurev-physiol-031920-092419","DOIUrl":"https://doi.org/10.1146/annurev-physiol-031920-092419","url":null,"abstract":"<p><p>Mitochondria are responsible for ATP production but are also known as regulators of cell death, and mitochondrial matrix Ca<sup>2+</sup> is a key modulator of both ATP production and cell death. Although mitochondrial Ca<sup>2+</sup> uptake and efflux have been studied for over 50 years, it is only in the past decade that the proteins responsible for mitochondrial Ca<sup>2+</sup> uptake and efflux have been identified. The identification of the mitochondrial Ca<sup>2+</sup> uniporter (MCU) led to an explosion of studies identifying regulators of the MCU. The levels of these regulators vary in a tissue- and disease-specific manner, providing new insight into how mitochondrial Ca<sup>2+</sup> is regulated. This review focuses on the proteins responsible for mitochondrial transport and what we have learned from mouse studies with genetic alterations in these proteins.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":18.2,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031920-092419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 17
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