Physiological genomicsPub Date : 2025-07-01Epub Date: 2025-04-04DOI: 10.1152/physiolgenomics.00050.2025
Utpal Sen
{"title":"Vacuole membrane protein 1 and miRNA-21: are they reliable partners to rescue acute kidney injury?","authors":"Utpal Sen","doi":"10.1152/physiolgenomics.00050.2025","DOIUrl":"10.1152/physiolgenomics.00050.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"406-408"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-07-01Epub Date: 2025-04-23DOI: 10.1152/physiolgenomics.00133.2024
Marissa A Lopez-Pier, Vito A Marino, Andrea C Vazquez-Loreto, Rinku S Skaria, Danielle K Cannon, Christina H Hoyer-Kimura, Alice E Solomon, Yulia Lipovka, Kevin Doubleday, Maricela Pier, Meinsung Chu, Rachel Mayfield, Samantha M Behunin, Tianjing Hu, Paul R Langlais, Timothy A McKinsey, John P Konhilas
{"title":"Myocardial transcriptomic and proteomic landscapes across the menopausal continuum in a murine model of chemically induced accelerated ovarian failure.","authors":"Marissa A Lopez-Pier, Vito A Marino, Andrea C Vazquez-Loreto, Rinku S Skaria, Danielle K Cannon, Christina H Hoyer-Kimura, Alice E Solomon, Yulia Lipovka, Kevin Doubleday, Maricela Pier, Meinsung Chu, Rachel Mayfield, Samantha M Behunin, Tianjing Hu, Paul R Langlais, Timothy A McKinsey, John P Konhilas","doi":"10.1152/physiolgenomics.00133.2024","DOIUrl":"10.1152/physiolgenomics.00133.2024","url":null,"abstract":"<p><p>Risk of cardiovascular disease (CVD) in women increases with the menopausal transition. Using a chemical model (4-vinylcyclohexene diepoxide; VCD) of accelerated ovarian failure, we previously demonstrated that menopausal females are more susceptible to CVD compared with peri- or premenopausal females like humans. Yet, the cellular and molecular mechanisms underlying this shift in CVD susceptibility across the pre- to peri- to menopause continuum remain understudied. In this work using the VCD mouse model, we phenotyped cellular and molecular signatures from hearts at each hormonally distinct stage that included transcriptomic, proteomic, and cell biological analyses. The transcriptional profile of premenopausal hearts clustered separately from perimenopausal and menopausal hearts, which clustered more similarly. Proteomics also revealed hormonal clustering; perimenopausal hearts grouped more closely with premenopausal than menopausal hearts. Both proteomes and transcriptomes showed similar trends in genes associated with atherothrombosis, contractility, and impaired nuclear signaling between pre-, peri-, and menopausal murine hearts. Further analysis of posttranslational modifications (PTMs) showed hormone-dependent shifts in the phosphoproteome and acetylome. To further interrogate these findings, we triggered pathological remodeling using angiotensin II (Ang II). Phosphorylation of AMP-activated protein kinase (AMPK) signaling and histone deacetylase (HDAC) activity were found to be dependent on hormonal status and Ang II stimulation. Finally, knockdown of anti-inflammatory regulatory T cells (Treg) exacerbated Ang II-dependent fibrosis implicating HDAC-mediated epigenetic suppression of Treg activity. Taken together, we demonstrated unique cellular and molecular profiles underlying the cardiac phenotype of pre-, peri-, and menopausal mice supporting the necessity to study CVD in females across the hormonal transition.<b>NEW & NOTEWORTHY</b> Cycling and perimenopausal females are protected from cardiovascular disease (CVD) whereas menopausal females are more susceptible to CVD and other pathological sequalae. The cellular and molecular mechanisms underlying loss of CVD protection across the pre- to peri- to menopause transition remain understudied. Using the murine 4-vinylcyclohexene diepoxide (VCD) model of menopause we highlight cellular and molecular signatures from hearts at each hormonally distinct stage that included transcriptomic, proteomic, and cell biological analyses.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"409-430"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-07-01Epub Date: 2025-04-04DOI: 10.1152/physiolgenomics.00047.2025
Brandon M Schickling, Mark K Santillan, Donna A Santillan
{"title":"Alternative splicing of CADM1 in preeclampsia: implications for endothelial dysfunction and offspring cardiovascular risk.","authors":"Brandon M Schickling, Mark K Santillan, Donna A Santillan","doi":"10.1152/physiolgenomics.00047.2025","DOIUrl":"10.1152/physiolgenomics.00047.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"403-405"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-06-01Epub Date: 2025-04-16DOI: 10.1152/physiolgenomics.00172.2024
Johanna Flodin, Stefan M Reitzner, Nida Mahmoud Hourani Soutari, Aisha S Ahmed, Li Guo, Nils-Krister Persson, Jovan P Antovic, Paul W Ackermann
{"title":"The acute effects of neuromuscular electrical stimulation on coagulation and cardiovascular factors.","authors":"Johanna Flodin, Stefan M Reitzner, Nida Mahmoud Hourani Soutari, Aisha S Ahmed, Li Guo, Nils-Krister Persson, Jovan P Antovic, Paul W Ackermann","doi":"10.1152/physiolgenomics.00172.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00172.2024","url":null,"abstract":"<p><p>Neuromuscular electrical stimulation (NMES) can potentially be used to prevent venous thromboembolism; however, its impact on coagulation-related factors remains poorly understood. We aimed to investigate the acute effects on coagulation- and cardiovascular factors immediately after a 2-h NMES session. Levels of overall hemostatic potential (OHP), fibrinogen, factor VIII, and Olink proteomic cardiovascular factors were assessed before and after the NMES session in 36 healthy participants (20 males and 16 females) with a mean age of 31.9 yr. NMES was administered using integrated textile electrodes in pants (NMES pants). Mean intensities during the quadriceps, hamstrings, and gluteus muscle stimulation were 16.5, 20.5, and 25.4 mA, respectively, corresponding to submaximal intensity levels with acceptable discomfort (just below 4 on the visual analogue scale [VAS], 0-10). The NMES session resulted in a significant increase in mean (SD) OHP [94.4 (28.3) to 103 (31.0)], and overall coagulation potential [292 (50.4) to 307(49.8)], and a decrease in overall fibrinolytic potential [68.2 (5.46) to 67.1 (5.20)]. These changes were highly correlated with the increase in fibrinogen (all <i>R</i> > 0.7, <i>P</i> ≤ 0.001), but not with the increase in factor VIII. In addition, 18 of 92 cardiovascular proteins, specifically those involved in regulating inflammation and extracellular matrix remodeling, were influenced by NMES; however, low correlations were found between the changes in these proteins and OHP analyses. In conclusion, the NMES session resulted in a slight increase in the coagulative state, mirroring that seen after a bout of regular exercise. The changes observed in cardiovascular factors, which are mostly not directly related to coagulation, suggest that NMES may subsequently modulate inflammatory responses, warranting further investigation.<b>NEW & NOTEWORTHY</b> The immediate response to a 2-h neuromuscular electrical stimulation (NMES) session, delivered at an acceptable level of discomfort using NMES-pants, marginally increases the coagulative state, similar to what is observed after regular physical exercise. This change is not expected to significantly increase the risk of blood clotting, as all factors remain within the normal reference range. Interestingly, NMES simultaneously appears to affect proteins that regulate the transition of inflammation into an anti-inflammatory response.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":"57 6","pages":"391-402"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-06-01Epub Date: 2025-03-25DOI: 10.1152/physiolgenomics.00043.2025
Victor Guryev
{"title":"Colonic responses to aspirin treatment: transcriptome effects by dose, time, and ancestry.","authors":"Victor Guryev","doi":"10.1152/physiolgenomics.00043.2025","DOIUrl":"10.1152/physiolgenomics.00043.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"383-384"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-06-01Epub Date: 2025-04-21DOI: 10.1152/physiolgenomics.00174.2024
Michael Marks-Hultström, Amanda M Marks, Guillaume Butler-Laporte, Satoshi Yoshiji, Tianyuan Lu, Dave R Morrison, Tomoko Nakanishi, Yiheng Chen, Vincenzo Forgetta, Yossi Farjoun, Robert Frithiof, Miklos Lipcsey, Hugo Zeberg, J Brent Richards
{"title":"A genetic variant associated with aquaporin 3 expression is correlated to in-hospital death in COVID-19 patients with extracellular hyperosmolality.","authors":"Michael Marks-Hultström, Amanda M Marks, Guillaume Butler-Laporte, Satoshi Yoshiji, Tianyuan Lu, Dave R Morrison, Tomoko Nakanishi, Yiheng Chen, Vincenzo Forgetta, Yossi Farjoun, Robert Frithiof, Miklos Lipcsey, Hugo Zeberg, J Brent Richards","doi":"10.1152/physiolgenomics.00174.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00174.2024","url":null,"abstract":"<p><p>Hyperosmolality is increasingly recognized as a factor contributing to severe COVID-19. Recently, a genetic variant near the aquaporin 3 (<i>AQP3</i>) water channel was associated with severe COVID-19 [rs60840586:G; odds ratio (OR): 1.07, <i>P</i> = 2.5 × 10<sup>-9</sup>]. The variant is known to increase gene expression of AQP3 in several organs, including the lung [normalized expression scores (NES) = 0.33, <i>P</i> = 4.1 × 10<sup>-20</sup>] in GTEx. In this study, we investigated 576 patients in the Biobanque Quebecoise de la COVID-19 (BQC-19) with both genetic and clinical data available. We estimated plasma osmolality using the formula: eOSM = 2 × [Na<sup>+</sup>] + 2 × [K<sup>+</sup>] + [Urea] + [Glucose]. Using a logistic regression of mortality against eOSM, genotype at rs60840586, sex, age, and the first 10 genetic principal components, we confirm that hyperosmolality is associated with COVID-19 mortality (OR = 2.06 [95% CI = 1.62-2.65], <i>P</i> = 9.13 × 10<sup>-9</sup>). Interestingly, we found that the risk of death linked to hyperosmolality is influenced by the <i>AQP3</i> variant rs60840586:G genotype (OR = 1.95 [95% CI = 1.22-3.28], <i>P</i> = 0.0075). However, the rs60840586 genotype did not independently affect mortality in this cohort. These findings suggest that the body's ability to regulate and accommodate hyperosmolality may be disrupted by overexpression of <i>AQP3</i>, potentially worsening outcomes in COVID-19. Given the role of AQP3 in water transport and homeostasis, further defining the functionality of its variants may provide key insights into COVID-19 severity and guide clinical management strategies, particularly in critically ill patients with hyperosmolality.<b>NEW & NOTEWORTHY</b> A genetic variant near water channel <i>AQP3</i>, linked to severe COVID-19, amplifies the risk of death in patients with elevated plasma osmolality. In patients hospitalized with COVID-19, we show that although the variant does not affect systemic osmolality directly, it interacts with hyperosmolality to increase mortality risk. These findings highlight a potential mechanism where AQP3 overexpression disrupts cellular water handling during critical illness, offering new insight into the role of water balance in COVID-19 pathophysiology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":"57 6","pages":"385-390"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological genomicsPub Date : 2025-06-01Epub Date: 2025-03-12DOI: 10.1152/physiolgenomics.00196.2024
Roman O Bokov, Kristina A Sharlo, Natalia A Vilchinskaya, Sergey A Tyganov, Olga V Turtikova, Sergey V Rozhkov, Ruslan M Deviatiiarov, Oleg A Gusev, Elena S Tomilovskaya, Boris S Shenkman, Oleg I Orlov
{"title":"Molecular insights into human soleus muscle atrophy development: long-term dry immersion effects on the transcriptomic profile and posttranslational signaling.","authors":"Roman O Bokov, Kristina A Sharlo, Natalia A Vilchinskaya, Sergey A Tyganov, Olga V Turtikova, Sergey V Rozhkov, Ruslan M Deviatiiarov, Oleg A Gusev, Elena S Tomilovskaya, Boris S Shenkman, Oleg I Orlov","doi":"10.1152/physiolgenomics.00196.2024","DOIUrl":"10.1152/physiolgenomics.00196.2024","url":null,"abstract":"<p><p>Muscle disuse results in complex signaling alterations followed by structural and functional changes, such as atrophy, force decrease, and slow-to-fast fiber-type shift. Little is known about human skeletal muscle signaling alterations under long-term muscle disuse. In this study, we describe the effects of 21-day dry immersion on human postural soleus muscle. We performed both transcriptomic analysis and Western blots to describe the states of the key signaling pathways regulating soleus muscle fiber size, fiber type, and metabolism. Twenty-one-day dry immersion resulted in both slow-type and fast-type myofibers atrophy, downregulation of rRNA content, and mTOR signaling. Twenty-one-day dry immersion also leads to slow-to-fast fiber-type and gene expression shift, upregulation of p-eEF2, p-CaMKII, p-ACC content and downregulation of NFATc1 nuclear content. It also caused massive gene expression alterations associated with calcium signaling, cytoskeletal parameters, and downregulated mitochondrial signaling (including fusion, fission, and marker of mitochondrial density).<b>NEW & NOTEWORTHY</b> The main findings of our study are as follows: <i>1</i>) The soleus slow fibers atrophy after 21-day dry immersion (DI) does not exceed that after 7-day DI; <i>2</i>) The soleus ubiquitin ligases expression after 21-day DI returns to its initial level; <i>3</i>) The soleus slow fibers atrophy after 21-day DI is accompanied by a mitochondrial apparatus structural markers decrease; <i>4</i>) The soleus fibers signaling pathways restructuring process during 21-day DI is carried out in a complex manner.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"357-382"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptomic responses of equine skeletal muscle to acute exercise in a hot environment.","authors":"Kenya Takahashi, Takanaga Shirai, Kazutaka Mukai, Yusaku Ebisuda, Fumi Sugiyama, Toshinobu Yoshida, Yu Kitaoka","doi":"10.1152/physiolgenomics.00200.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00200.2024","url":null,"abstract":"<p><p>While exercise performance deteriorates in hot environments, heat stress may contribute to exercise-induced adaptations in skeletal muscle. In this study, we assessed transcriptional profiles of equine skeletal muscle following 3 min of high-intensity exercise (at the speed eliciting their maximal oxygen uptake) in cool (Wet Bulb Globe Temperature [WBGT] 15°C) or hot (WBGT 30°C) conditions. Differential gene expression was identified using DESeq2 (false discovery rate cutoff: 0.05, minimal fold change: 1.5). At 4 h after exercise, RNA-seq identified 176 and 156 genes that were differentially expressed in the middle gluteal muscle in hot and cool conditions, respectively. Of these genes, 110 genes were altered in both conditions, whereas 66 genes were only responsive to exercise in the hot condition. Between the two environmental conditions, the expression of only one gene (KANK1) was higher in the hot condition compared with the cool condition. Pathway analysis revealed that the response to temperature stimulus was upregulated only after exercise in the hot condition. Although the overall transcriptional response to exercise was similar in both environmental conditions, our results provide insight into the molecular mechanisms of equine skeletal muscle adaptation to heat acclimation.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Buyan-Ochir Orgil, Fuyi Xu, Ning Li, Akhilesh K Bajpai, Neely R Alberson, Jason N Johnson, Qingqing Gu, Glenn T Wetzel, Jeffrey A Towbin, Lu Lu, Enkhsaikhan Purevjav
{"title":"Genetic mapping of electrocardiographic parameters in BXD strains reveals Chromosome 3 loci to be associated with cardiac repolarization abnormalities.","authors":"Buyan-Ochir Orgil, Fuyi Xu, Ning Li, Akhilesh K Bajpai, Neely R Alberson, Jason N Johnson, Qingqing Gu, Glenn T Wetzel, Jeffrey A Towbin, Lu Lu, Enkhsaikhan Purevjav","doi":"10.1152/physiolgenomics.00183.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00183.2024","url":null,"abstract":"<p><p><b>Background:</b> Risk factors for cardiac arrhythmias that can cause sudden death and heart failure include genetics, age, lifestyle, and other environmental factors. <b>Objectives:</b> The study assessed electrocardiography (ECG) traits in BXD mice and explored associated quantitative trait loci (QTLs). <b>Methods:</b> Five-minute electrocardiograms were recorded in 44 BXD strains at 4-5 months of age (<i>n</i>≥5 mice/sex/strain). ECG and arrhythmia traits were associated with echocardiography, blood pressure, genome and heart transcriptome data followed by expression QTL mapping. <b>Results:</b> A significant variability in ECG parameters and arrhythmias were recorded among BXDs. Among male BXDs, QRS duration was significantly associated with increased left ventricular internal diameter (LVID) and reduced ejection fraction and fractional shortening, while premature ventricular contractions (PVCs) were correlated with LVID, LV volumes and pulmonary vein peak pressure. In female BXDs, PVCs and premature atrial contractions (PACs) significantly related with right ventricular ID and cardiac output. One significant QTL associated with QTc and JT durations was identified on Chromosome (Chr) 3 in male BXDs, while Chr 9 locus was suggestive for association with QTc and QT intervals in female mice. <i>Gon4l</i> was predicted as a strong candidate gene associated with repolarization abnormalities including short or long QT syndromes in humans. <b>Conclusions:</b> Study results suggested an influence of genetic background on expression of ECG parameters and arrhythmias based on significant variations of those traits between mouse strains of the BXD family. We conclude that murine BXD family can serve as a valuable reference for systems biology and comparative predictions of arrhythmia disorders.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}