Function (Oxford, England)最新文献_第3页

Megalin Knockout Reduces SGLT2 Expression and Sensitizes to Western Diet-induced Kidney Injury. Megalin基因敲除可减少SGLT2的表达，并对西方饮食诱导的肾损伤敏感。

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae026

Elynna B Youm, Katherine E Shipman, Wafaa N Albalawy, Amber M Vandevender, Ian J Sipula, Youssef Rbaibi, Allison E Marciszyn, Jared A Lashway, Emma E Brown, Corry B Bondi, Cary R Boyd-Shiwarski, Roderick J Tan, Michael J Jurczak, Ora A Weisz

{"title":"Megalin Knockout Reduces SGLT2 Expression and Sensitizes to Western Diet-induced Kidney Injury.","authors":"Elynna B Youm, Katherine E Shipman, Wafaa N Albalawy, Amber M Vandevender, Ian J Sipula, Youssef Rbaibi, Allison E Marciszyn, Jared A Lashway, Emma E Brown, Corry B Bondi, Cary R Boyd-Shiwarski, Roderick J Tan, Michael J Jurczak, Ora A Weisz","doi":"10.1093/function/zqae026","DOIUrl":"10.1093/function/zqae026","url":null,"abstract":"Megalin (Lrp2) is a multiligand receptor that drives endocytic flux in the kidney proximal tubule (PT) and is necessary for the recovery of albumin and other filtered proteins that escape the glomerular filtration barrier. Studies in our lab have shown that knockout (KO) of Lrp2 in opossum PT cells leads to a dramatic reduction in sodium-glucose co-transporter 2 (SGLT2) transcript and protein levels, as well as differential expression of genes involved in mitochondrial and metabolic function. SGLT2 transcript levels are reduced more modestly in Lrp2 KO mice. Here, we investigated the effects of Lrp2 KO on kidney function and health in mice fed regular chow (RC) or a Western-style diet (WD) high in fat and refined sugar. Despite a modest reduction in SGLT2 expression, Lrp2 KO mice on either diet showed increased glucose tolerance compared to control mice. Moreover, Lrp2 KO mice were protected against WD-induced fat gain. Surprisingly, renal function in male Lrp2 KO mice on WD was compromised, and the mice exhibited significant kidney injury compared with control mice on WD. Female Lrp2 KO mice were less susceptible to WD-induced kidney injury than male Lrp2 KO. Together, our findings reveal both positive and negative contributions of megalin expression to metabolic health, and highlight a megalin-mediated sex-dependent response to injury following WD.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565332","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: 0

Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue. 胆固醇酯转移蛋白 (CETP) 对血管周围脂肪组织的性别特异性影响

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae024

C M Lazaro, I N Freitas, V S Nunes, D M Guizoni, J A Victorio, H C F Oliveira, A P Davel

{"title":"Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue.","authors":"C M Lazaro, I N Freitas, V S Nunes, D M Guizoni, J A Victorio, H C F Oliveira, A P Davel","doi":"10.1093/function/zqae024","DOIUrl":"10.1093/function/zqae024","url":null,"abstract":"Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored. Here, we hypothesized that CETP impacts the perivascular adipose tissue (PVAT) phenotype and function in a sex-specific manner. PVAT function, gene and protein expression, and morphology were examined in male and female transgenic mice expressing human or simian CETP and their non-transgenic counterparts (NTg). PVAT exerted its anticontractile effect in aortas from NTg males, NTg females, and CETP females, but not in CETP males. CETP male PVAT had reduced NO levels, decreased eNOS and phospho-eNOS levels, oxidative stress, increased NOX1 and 2, and decreased SOD2 and 3 expressions. In contrast, CETP-expressing female PVAT displayed increased NO and phospho-eNOS levels with unchanged NOX expression. NOX inhibition and the antioxidant tempol restored PVAT anticontractile function in CETP males. Ex vivo estrogen treatment also restored PVAT function in CETP males. Moreover, CETP males, but not female PVAT, show increased inflammatory markers. PVAT lipid content increased in CETP males but decreased in CETP females, while PVAT cholesterol content increased in CETP females. CETP male PVAT exhibited elevated leptin and reduced Prdm16 (brown adipocyte marker) expression. These findings highlight CETP sex-specific impact on PVAT. In males, CETP impaired PVAT anticontractile function, accompanied by oxidative stress, inflammation, and whitening. Conversely, in females, CETP expression increased NO levels, induced an anti-inflammatory phenotype, and preserved the anticontractile function. This study reveals sex-specific vascular dysfunction mediated by CETP.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565333","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: 0

Single Cell RNAseq Analysis of Cytokine-Treated Human Islets: Association of Cellular Stress with Impaired Cytokine Responsiveness. 细胞因子处理的人类胰岛的单细胞 RNAseq 分析：细胞压力与细胞因子反应能力受损的关系

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae015

Jennifer S Stancill, Moujtaba Y Kasmani, Weiguo Cui, John A Corbett

{"title":"Single Cell RNAseq Analysis of Cytokine-Treated Human Islets: Association of Cellular Stress with Impaired Cytokine Responsiveness.","authors":"Jennifer S Stancill, Moujtaba Y Kasmani, Weiguo Cui, John A Corbett","doi":"10.1093/function/zqae015","DOIUrl":"10.1093/function/zqae015","url":null,"abstract":"Pancreatic β-cells are essential for survival, being the only cell type capable of insulin secretion. While they are believed to be vulnerable to damage by inflammatory cytokines such as interleukin-1 beta (IL-1β) and interferon-gamma, we have recently identified physiological roles for cytokine signaling in rodent β-cells that include the stimulation of antiviral and antimicrobial gene expression and the inhibition of viral replication. In this study, we examine cytokine-stimulated changes in gene expression in human islets using single-cell RNA sequencing. Surprisingly, the global responses of human islets to cytokine exposure were remarkably blunted compared to our previous observations in the mouse. The small population of human islet cells that were cytokine responsive exhibited increased expression of IL-1β-stimulated antiviral guanylate-binding proteins, just like in the mouse. Most human islet cells were not responsive to cytokines, and this lack of responsiveness was associated with high expression of genes encoding ribosomal proteins. We further correlated the expression levels of RPL5 with stress response genes, and when expressed at high levels, RPL5 is predictive of failure to respond to cytokines in all endocrine cells. We postulate that donor causes of death and isolation methodologies may contribute to stress of the islet preparation. Our findings indicate that activation of stress responses in human islets limits cytokine-stimulated gene expression, and we urge caution in the evaluation of studies that have examined cytokine-stimulated gene expression in human islets without evaluation of stress-related gene expression.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565334","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: 0

Brain Ballet: The Choreography of Left-Right Neuroendocrine Signals in Injury. 大脑芭蕾：损伤中左右神经内分泌信号的编排。

IF 5.1

Function (Oxford, England) Pub Date : 2024-07-11 DOI: 10.1093/function/zqae022

Marshall T Holland, Bryan Becker

引用次数: 0

Society Note - 'How Do We Clean Up the Scientific Record?' 社会说明--"我们如何清理科学记录？

IF 5.1

Function (Oxford, England) Pub Date : 2024-06-11 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqae028

引用次数: 0

Rethinking Ischemic Acute Kidney Injury as Nephrotoxicity. 将缺血性急性肾损伤视为肾毒性的再思考

Function (Oxford, England) Pub Date : 2024-04-17 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqae020

David M Pollock

引用次数: 0

High Salt Remodels Kidney Metabolism: Metabolite Fuel, Fate, and Signals. 高盐重塑肾脏代谢：代谢物燃料、命运和信号

Function (Oxford, England) Pub Date : 2024-01-29 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqae006

Moritz Lassé, Markus M Rinschen

引用次数: 0

Epigenetic Regulation of Autophagy in Bone Metabolism. 骨代谢中自噬的表观遗传调控

Function (Oxford, England) Pub Date : 2024-01-27 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqae004

Yazhou Zhang, Qianqian Wang, Hongjia Xue, Yujin Guo, Shanshan Wei, Fengfeng Li, Linqiang Gong, Weiliang Pan, Pei Jiang

{"title":"Epigenetic Regulation of Autophagy in Bone Metabolism.","authors":"Yazhou Zhang, Qianqian Wang, Hongjia Xue, Yujin Guo, Shanshan Wei, Fengfeng Li, Linqiang Gong, Weiliang Pan, Pei Jiang","doi":"10.1093/function/zqae004","DOIUrl":"10.1093/function/zqae004","url":null,"abstract":"The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's impact on bone health varies depending on factors such as regulation, cell type, environmental cues, and physiological context. Despite being traditionally considered a cytoplasmic process, autophagy is subject to transcriptional and epigenetic regulation within the nucleus. However, the precise influence of epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNA expression, on cellular fate remains incompletely understood. The interplay between autophagy and epigenetic modifications adds complexity to bone cell regulation. This article provides an in-depth exploration of the intricate interplay between these two regulatory paradigms, with a focus on the epigenetic control of autophagy in bone metabolism. Such an understanding enhances our knowledge of bone metabolism-related disorders and offers insights for the development of targeted therapeutic strategies.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133412","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: 0

Plasma of COVID-19 Patients Does Not Alter Electrical Resistance of Human Endothelial Blood-Brain Barrier In Vitro. COVID-19 患者的血浆不会改变体外人类内皮血脑屏障的抗电性

Function (Oxford, England) Pub Date : 2024-01-09 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqae002

Agnė Pociūtė, Karolina Kriaučiūnaitė, Aida Kaušylė, Birutė Zablockienė, Tadas Alčauskas, Augustė Jelinskaitė, Akvilė Rudėnaitė, Ligita Jančorienė, Saulius Ročka, Alexei Verkhratsky, Augustas Pivoriūnas

{"title":"Plasma of COVID-19 Patients Does Not Alter Electrical Resistance of Human Endothelial Blood-Brain Barrier In Vitro.","authors":"Agnė Pociūtė, Karolina Kriaučiūnaitė, Aida Kaušylė, Birutė Zablockienė, Tadas Alčauskas, Augustė Jelinskaitė, Akvilė Rudėnaitė, Ligita Jančorienė, Saulius Ročka, Alexei Verkhratsky, Augustas Pivoriūnas","doi":"10.1093/function/zqae002","DOIUrl":"10.1093/function/zqae002","url":null,"abstract":"The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study, we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon γ-induced protein 10 kDa, hepatocyte growth factor, and interleukin-18 in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not affect BBB paracellular pathway directly and suggest that pathological remodeling (if any) of BBB during COVID-19 may occur through indirect or yet unknown mechanisms.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133414","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: 0

Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease. 阿尔茨海默氏症小鼠模型的神经肌肉功能障碍先于认知功能受损

IF 5.1

Function (Oxford, England) Pub Date : 2023-12-04 eCollection Date: 2024-01-01 DOI: 10.1093/function/zqad066

Matthew H Brisendine, Anna S Nichenko, Aloka B Bandara, Orion S Willoughby, Niloufar Amiri, Zach Weingrad, Kalyn S Specht, Jacob M Bond, Adele Addington, Ronald G Jones, Kevin A Murach, Steven Poelzing, Siobhan M Craige, Robert W Grange, Joshua C Drake

{"title":"Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease.","authors":"Matthew H Brisendine, Anna S Nichenko, Aloka B Bandara, Orion S Willoughby, Niloufar Amiri, Zach Weingrad, Kalyn S Specht, Jacob M Bond, Adele Addington, Ronald G Jones, Kevin A Murach, Steven Poelzing, Siobhan M Craige, Robert W Grange, Joshua C Drake","doi":"10.1093/function/zqad066","DOIUrl":"10.1093/function/zqad066","url":null,"abstract":"Alzheimer's disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur years earlier in those that develop AD; however, it is unknown what causes these peripheral phenotypes in a disease of the brain. Exercise promotes muscle, mitochondria, and cognitive health and is proposed to be a potential therapeutic for AD, but no study has investigated how skeletal muscle adapts to exercise training in an AD-like context. Utilizing 5xFAD mice, an AD model that develops ad-like pathology and cognitive impairments around 6 mo of age, we examined in vivo neuromuscular function and exercise adapations (mitochondrial respiration and RNA sequencing) before the manifestation of overt cognitive impairment. We found 5xFAD mice develop neuromuscular dysfunction beginning as early as 4 mo of age, characterized by impaired nerve-stimulated muscle torque production and compound nerve action potential of the sciatic nerve. Furthermore, skeletal muscle in 5xFAD mice had altered, sex-dependent, adaptive responses (mitochondrial respiration and gene expression) to exercise training in the absence of overt cognitive impairment. Changes in peripheral systems, specifically neural communication to skeletal muscle, may be harbingers for AD and have implications for lifestyle interventions, like exercise, in AD.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10727840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814640","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: 0