Function (Oxford, England)最新文献_第3页

Renal Implications of Kappa Opioid Receptor Signaling in Sprague-Dawley Rats. Sprague-Dawley大鼠Kappa阿片受体信号对肾脏的影响。

IF 3.8

Function (Oxford, England) Pub Date : 2025-08-01 DOI: 10.1093/function/zqaf028

Steven Didik, Daria Golosova, Adrian Zietara, Ruslan Bohovyk, Ameneh Ahrari, Vladislav Levchenko, Olha Kravtsova, Krish Taneja, Sherif Khedr, Marharyta Semenikhina, Oleg Palygin, Alexander Staruschenko

{"title":"Renal Implications of Kappa Opioid Receptor Signaling in Sprague-Dawley Rats.","authors":"Steven Didik, Daria Golosova, Adrian Zietara, Ruslan Bohovyk, Ameneh Ahrari, Vladislav Levchenko, Olha Kravtsova, Krish Taneja, Sherif Khedr, Marharyta Semenikhina, Oleg Palygin, Alexander Staruschenko","doi":"10.1093/function/zqaf028","DOIUrl":"10.1093/function/zqaf028","url":null,"abstract":"Opioid use for pain management and illicit consumption has been associated with adverse cardiovascular and cardiorenal outcomes. Despite these associations, the mechanisms underlying opioid-induced kidney damage remain poorly understood. Recently, we demonstrated that stimulation of kappa opioid receptors (KOR) is implicated in the aggravation of salt-sensitive hypertension, glomerular injury, and podocyte damage through excessive podocyte calcium influx. This study aims to elucidate the KOR signaling and renal outcomes underlying opioid use in Sprague-Dawley (SD) rats. Here, we employed freshly isolated glomeruli from SD male rats and immortalized human podocyte cell cultures to investigate the role of KORs in podocyte calcium regulation and overall glomerular function. A glomerular permeability assay was used to evaluate the impact of KORs on glomerular filter integrity. Additionally, the long-term effects of KOR activation were assessed in vivo by chronic intravenous infusion of selective KOR agonist BRL 52537 in SD rats. We found that acute application of BRL 52537 resulted in increased plasma membrane ion channel activity in immortalized human podocytes. Significant calcium influx in response to BRL 52537 was detected in podocytes of the isolated SD rat glomeruli. Further, glomerular permeability analysis revealed increased permeability and impaired filter integrity, indicating altered glomerular function. Lastly, prolonged KOR activation in SD rats results in an increase in blood pressure, an elevation of basal calcium levels in podocytes, and albuminuria. In conclusion, this study identifies novel renal physiological mechanisms through which opioid-induced KOR activation contributes to podocyte injury and glomerular damage in SD rats.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531426","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

The Microenvironment in Focus for Male Fertility. 微环境是男性生育能力的焦点。

IF 3.8

Function (Oxford, England) Pub Date : 2025-08-01 DOI: 10.1093/function/zqaf027

Helle Praetorius

引用次数: 0

Distinct Right Ventricular Performance in Response to Acute Colchicine Treatment in Healthy and Diseased States. 健康和患病状态下秋水仙碱急性治疗后的不同右心室表现。

IF 3.8

Function (Oxford, England) Pub Date : 2025-08-01 DOI: 10.1093/function/zqaf021

Kristen LeBar, Lalida Tantisuwat, Jassia Pang, Adam J Chicco, Naomi C Chesler, Zhijie Wang

{"title":"Distinct Right Ventricular Performance in Response to Acute Colchicine Treatment in Healthy and Diseased States.","authors":"Kristen LeBar, Lalida Tantisuwat, Jassia Pang, Adam J Chicco, Naomi C Chesler, Zhijie Wang","doi":"10.1093/function/zqaf021","DOIUrl":"10.1093/function/zqaf021","url":null,"abstract":"Right ventricular (RV) dysfunction is a major contributor to mortality in several cardiopulmonary diseases. However, the understanding of RV pathophysiology falls behind its left counterpart, limiting treatment options for conditions associated with discrete RV dysfunction and failure, such as pulmonary hypertension (PH). Accumulating evidence suggests that colchicine (COL) may have therapeutic benefits in multiple diseases, including PH. The mechanisms by which COL improves cardiovascular function are incompletely understood but may be associated with reductions in myocardial tissue viscoelasticity via microtubule depolymerization as demonstrated in prior ex vivo studies. The aim of this study is to investigate the impact of acute COL treatment on healthy and diseased RV organ function. Healthy and PH rats were anesthetized and catheterized for investigation of RV pressure-volume (PV) relationships before and after intramyocardial injections of COL. Marked RV failure was observed secondary to PH, characterized by elevated pulmonary vascular resistance (PVR), RV pressures, and end diastolic PV relation (EDPVR) with reduced RV compliance, preload and stroke volume. COL reversed pathological changes in parameters such as EDPVR, and improved RV preload, compliance, stroke volume and ejection fraction in PH rats. COL also reduced RV systolic pressure and heart rate in PH rats, which may be associated with broader effects of COL (improved PVR) in addition to myocardial viscoelastic reduction. In contrast, no significant effect on cardiopulmonary function was observed in healthy rats. These results highlight a potential contribution of RV viscoelasticity to ventricular dysfunction, implicating tissue viscoelasticity as a therapeutic target for RV failure patients.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710064","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

Sphingosine-1-Phosphate Receptor 2 Promotes Renal Microvascular Constriction and Kidney Injury Following Renal Ischemia-Reperfusion in Rats. 鞘氨醇-1-磷酸受体2促进大鼠肾缺血再灌注后肾微血管收缩和肾损伤。

IF 5.1

Function (Oxford, England) Pub Date : 2025-06-19 DOI: 10.1093/function/zqaf024

Zhengrong Guan, Colton E Remedies, Yanfeng Zhang, Paul W Sanders, Edward W Inscho, Wenguang Feng

{"title":"Sphingosine-1-Phosphate Receptor 2 Promotes Renal Microvascular Constriction and Kidney Injury Following Renal Ischemia-Reperfusion in Rats.","authors":"Zhengrong Guan, Colton E Remedies, Yanfeng Zhang, Paul W Sanders, Edward W Inscho, Wenguang Feng","doi":"10.1093/function/zqaf024","DOIUrl":"10.1093/function/zqaf024","url":null,"abstract":"Ischemia-reperfusion (IR) induced acute kidney injury (AKI) features increased renal vascular resistance, which is predominantly regulated by adjustments in afferent arteriolar diameter. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is a potent vasoconstrictor in afferent arterioles. We hypothesized that IR enhanced afferent arteriolar sensitivity to S1P-induced vasoconstriction, thus contributing to renal microvascular dysfunction and kidney injury in AKI. The impact of IR on afferent arteriolar reactivity to S1P was assessed using the in vitro blood-perfused juxtamedullary nephron preparation in male rats subjected to 60 min of bilateral renal arterial ischemia followed by 24 h of reperfusion. Baseline diameter of afferent arterioles declined significantly following IR. S1P evoked concentration-dependent vasoconstriction in both sham and IR rats. However, the S1P concentration-response curve left-shifted after IR and its EC50 reduced by 8-fold (P < 0.05), suggesting enhanced afferent arteriolar reactivity to S1P. S1P receptor 2 (S1PR2) blockade with JTE-013 increased arteriolar diameter by 38 ± 7% following IR contrasted to a 9 ± 3% increase in sham rats (P < 0.05), indicating that endogenous S1P exerts a significant impact on afferent arteriolar tone after IR. Furthermore, IR upregulated mRNA and protein of S1PR2 in isolated preglomerular microvessels and elevated S1P content in kidney homogenates. Conversely, following IR, vasoresponsiveness to S1PR1 agonist, sphingosine, endothelin-1, norepinephrine, and angiotensin II did not differ from sham controls. JTE-013 treatment reduced plasma creatinine, tubular damage, and kidney ROS accumulation in IR rats. These data establish that IR enhances renal microvascular S1P-S1PR2 signaling and promotes kidney sphingolipid metabolites that could negatively affect kidney tissue perfusion, leading to AKI.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251169","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

Proton-Secreting Cells as Drivers of Inflammation and Sperm Dysfunction in LPS-Induced Epididymitis. 在lps诱导的附睾炎中，质子分泌细胞是炎症和精子功能障碍的驱动因素。

IF 5.1

Function (Oxford, England) Pub Date : 2025-05-19 DOI: 10.1093/function/zqaf023

A A S Da Silva, F Barrachina, M C Avenatti, M L Elizagaray, I Bastepe, E Sasso-Cerri, M A Battistone

{"title":"Proton-Secreting Cells as Drivers of Inflammation and Sperm Dysfunction in LPS-Induced Epididymitis.","authors":"A A S Da Silva, F Barrachina, M C Avenatti, M L Elizagaray, I Bastepe, E Sasso-Cerri, M A Battistone","doi":"10.1093/function/zqaf023","DOIUrl":"10.1093/function/zqaf023","url":null,"abstract":"Proton-secreting cells in various organs, such as the kidney and epididymis, regulate pH balance, maintain cellular homeostasis, and support key physiological processes. More recently, these specialized cells have emerged as key contributors to mucosal immunity, orchestrating immune activation. Epididymitis is an inflammatory condition that significantly impacts male fertility, often due to a lack of diagnosis and treatment. This study investigates the role of region-specific epididymal proton-secreting clear cells (CCs) in shaping immune responses during LPS-induced epididymitis in mice. We found that in response to lipopolysaccharide (LPS), CCs rapidly shifted to a proinflammatory phenotype, marked by the upregulation of cytokines and chemokines, alongside the downregulation of genes involved in sperm maturation. Morphological changes in CCs, including increased apical blebs and altered shape across different epididymal segments, suggest their active role in immune responses. Moreover, mononuclear phagocytes reduced their luminal-reaching projections in the proximal epididymis after the LPS challenge. This bacterial antigen triggered dendritic cell migration and neutrophil infiltration in the distal epididymis. These immune landscape alterations contributed to epithelial damage and impaired sperm maturation, as evidenced by decreased sperm motility following LPS intravasal-epididymal injection. Our findings indicate that proton-secreting cells are immune gatekeepers in the epididymis, initiating immune responses and disrupting sperm maturation. This research enhances the understanding of epithelial immunoregulation and will help to develop novel diagnostic and therapeutic strategies for epididymitis and male infertility. Furthermore, insights into CC-mediated immune responses could inform the development of new approaches for male contraception.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210408","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

Activation of the Carotid Body by Kappa Opioid Receptors Mitigates Fentanyl-Induced Respiratory Depression. kappa阿片受体激活颈动脉体减轻芬太尼诱导的呼吸抑制。

IF 5.1

Function (Oxford, England) Pub Date : 2025-05-19 DOI: 10.1093/function/zqaf020

Ying-Jie Peng, Jayasri Nanduri, Ning Wang, Zheng Xie, Aaron P Fox, Nanduri R Prabhakar

{"title":"Activation of the Carotid Body by Kappa Opioid Receptors Mitigates Fentanyl-Induced Respiratory Depression.","authors":"Ying-Jie Peng, Jayasri Nanduri, Ning Wang, Zheng Xie, Aaron P Fox, Nanduri R Prabhakar","doi":"10.1093/function/zqaf020","DOIUrl":"10.1093/function/zqaf020","url":null,"abstract":"Previous studies reported that opioids depress breathing by inhibiting respiratory neural networks in the brainstem. The effects of opioids on sensory inputs regulating breathing are less studied. This study examined the effects of fentanyl and sufentanil on carotid body neural activity, a crucial sensory regulator of breathing. Both opioids stimulated carotid body afferent nerve activity and increased glomus cell [Ca2+]i levels. RNA sequencing and immunohistochemistry revealed a high abundance of κ opioid receptors (KORs) in carotid bodies, but no µ or δ opioid receptors. A KOR agonist, like fentanyl, stimulated carotid body afferents, while a KOR antagonist blocked carotid body activation by fentanyl and KOR agonist. In unanesthetized rats, fentanyl initially stimulated breathing, followed by respiratory depression. A KOR agonist stimulated breathing without respiratory inhibition, and this effect was absent in carotid body-denervated rats. Combining fentanyl with a KOR agonist attenuated respiratory depression in rats with intact carotid body but not in carotid body-denervated rats. These findings highlight previously uncharacterized activation of carotid body afferents by fentanyl via KORs as opposed to depression of brainstem respiratory neurons by µ opioid receptors and suggest that KOR agonists might counteract the central depressive effects of opioids on breathing.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082540","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

Moving Beyond Barker's Hypothesis Towards New Therapies for the Treatment of Fetal Growth Restriction. 超越巴克的假设，寻找治疗胎儿生长受限的新疗法。

IF 5.1

Function (Oxford, England) Pub Date : 2025-05-19 DOI: 10.1093/function/zqaf022

Laura E Coats, Barbara T Alexander

引用次数: 0

Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism. 有氧能力和运动通过增强胆汁酸代谢介导对肝脂肪变性的保护。

IF 5.1

Function (Oxford, England) Pub Date : 2025-05-19 DOI: 10.1093/function/zqaf019

Benjamin A Kugler, Adrianna Maurer, Xiaorong Fu, Edziu Franczak, Nick Ernst, Kevin Schwartze, Julie Allen, Tiangang Li, Peter A Crawford, Lauren G Koch, Steven L Britton, Kartik Shankar, Shawn C Burgess, John P Thyfault

{"title":"Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism.","authors":"Benjamin A Kugler, Adrianna Maurer, Xiaorong Fu, Edziu Franczak, Nick Ernst, Kevin Schwartze, Julie Allen, Tiangang Li, Peter A Crawford, Lauren G Koch, Steven L Britton, Kartik Shankar, Shawn C Burgess, John P Thyfault","doi":"10.1093/function/zqaf019","DOIUrl":"10.1093/function/zqaf019","url":null,"abstract":"High cardiorespiratory fitness and exercise show evidence of altering bile acid (BA) metabolism and are known to protect or treat diet-induced hepatic steatosis, respectively. Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of 2H2O. We also leveraged mice with inducible liver-specific deletion of Cyp7a1 (LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis. The synthesis of hepatic BA, cholesterol, and de novo lipogenesis was measured in rats bred for either high (HCR) or low (LCR) aerobic capacity consuming acute and chronic high-fat diets. HCR rats had increased synthesis of cholesterol and certain BA species in the liver compared to LCR rats. We also found that chronic exercise with voluntary wheel running (VWR) (4 weeks) increased newly synthesized BAs of specific species in male C57BL/6J mice compared to sedentary mice. Loss of Cyp7a1 resulted in fewer new BAs and increased liver triglycerides compared to controls after a 10-week high-fat diet. Additionally, exercise via VWR for 4 weeks effectively reduced hepatic triglycerides in the high-fat diet-fed control male and female mice as expected; however, exercise in LCyp7a1KO mice did not lower liver triglycerides in either sex. These results show that aerobic capacity and exercise increase hepatic BA metabolism, which may be critical for combatting hepatic steatosis.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804996","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

Science Is at a Crossroads-and Physiology With It: A Statement from the APS Chief Executive Officer. 科学和生理学正处于十字路口：美国科学学会首席执行官的声明。

IF 5.1

Function (Oxford, England) Pub Date : 2025-05-19 DOI: 10.1093/function/zqaf025

Scott Steen

引用次数: 0

A Perspective on "Signal Transduction Pathway Mediating Carotid Body Dependent Sympathetic Activation and Hypertension by Chronic Intermittent Hypoxia". 关于 "介导颈动脉体依赖性交感神经激活和慢性间歇性缺氧引起的高血压的信号转导途径 "的观点。

IF 5.1

Function (Oxford, England) Pub Date : 2025-03-24 DOI: 10.1093/function/zqaf012

Gary C Sieck

引用次数: 0