Dataset Information

Exercise sensitizes the pressure diuresis response: shifting immune landscapes underlie renal adaptations to exercise

ABSTRACT: Background: Exercise benefits several physiological systems to confer health; however, the mechanisms by which exercise impacts renal health remain poorly understood. Studies show moderate intensity exercise slows the age-related decline in kidney function. Additionally, exercise protects against AKI in several rodent models. We hypothesize that exercise triggers adaptative responses, which preserve hemodynamic balance in the kidneys under stress. Methods: We evaluated exercise-induced adaptations in 10–14-wk-old C57BL/6J male and female mice subjected to either 4 wk of voluntary wheel running or up to 2 wk of forced treadmill running (70% capacity for 40 min/d). Additionally, we evaluated endpoints 24 h after a single bout of exhaustive exercise to discern acute responses from chronic adaptations. We evaluated renal perfusion with contrast-enhanced ultrasound and assessed kidney function by measuring the ability to clear a volume load. Additionally, we performed flow cytometry, cytokine array, histopathology, and bulk mRNA sequencing to evaluate exercise-induced changes in the kidney. Results: We found a significant increase in the maximum steady state tissue contrast intensity in the kidneys of exercised male mice vs sedentary controls. Additionally, exercised male, but not female, mice excreted significantly more urine in the first hour after administration of a saline bolus. At the cellular level, we observed a significant increase in kidney resident macrophages (KRMs; CD45+CD11b+F4/80hi) after exercise training in male, but not female, mice. Because the macrophages were primarily CX3CR1+CCR2-, this suggests expansion of KRMs as the source of the increase. Lastly, bulk mRNA sequencing suggested exercise induces changes relating to water and sodium handling as well as angiogenesis and wound healing. Conclusions: These data suggest that exercise alters the immune landscape of the kidney, which may promote angiogenesis to increase renal microvasculature and improve sensitivity of the pressure diuresis response. Future studies will identify if macrophages cause the functional adaptations observed.

ORGANISM(S): Mus musculus

PROVIDER: GSE297842 | GEO | 2025/09/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Ischemic heart disease (IHD) remains a leading cause of mortality worldwide, often culminating in myocardial infarction (MI) and subsequent heart failure due to adverse fibrotic remodeling of the myocardium. Despite the lack of effective treatments, exercise has emerged as a promising strategy to reduce mortality risk and improve cardiac function post-MI. This study investigates the molecular mechanisms underlying exercise-induced cardioprotection by analyzing changes in several key cardiac cell populations after MI in a murine model. We assessed the effect of exercise preconditioning in mouse MI model through echocardiography, followed by single nuclei RNA-seq of cardiac cells, and validation by microscopy and flow cytometry. Our findings demonstrate that exercise significantly enhances cardiac function post-MI, as evidenced by improved ejection fraction and stroke volume in exercised mice. These improvements are linked to adaptive changes across multiple cardiac cell types. Notably, in infarcted mice, exercise caused a downregulation of cardiomyopathy-associated pathways, accompanied by changes in ECs, macrophages, fibroblasts and cardiomyocytes. Exercise stimulated formation of new capillaries which post-MI resulted in a more vascularized infarct border zone. Additionally, exercised hearts displayed a shift in macrophage populations towards a pro-regenerative phenotype, marked by an increase in resident CCR2- macrophages and a reduction in pro-inflammatory M1-gene expression. In cardiomyocytes, exercise enhanced pathways related to endothelial support and ATP biosynthesis, mitigating the upregulation of cardiomyopathy-associated pathways observed post-MI. Importantly, exercise also restored calcium signaling and reversed pathological potassium signaling, thereby preserving contractile function. Fibroblast analysis revealed that exercise stimulated activation of these cells to participate in scar formation. In conclusion, this study provides new insights into the cellular and molecular mechanisms through which exercise enhances cardiac function and provides cardio-protection post-MI, offering potential avenues for targeted therapies in patients with IHD.

Project description:We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180°.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and αB-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and αB-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and αB-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE naïve volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation. 16 healthy male subjects were recruited and attended the laboratory fasted on 4 consecutive days. Biopsies from the vastus lateralis muscle were obtained on Days 0, 1 and 3, with total RNA extracted for gene expression analysis by microarray. During this period, 8 subjects performed isokinetic leg extension exercise using an isokinetic dynamometer (180 degrees per second; maximum intensity) on two occassions (days 0 and 2). Data for 7 exercise subjects presented in this study. 8 further subjects acted as non-exercised controls and did not participate in any exercise during the study period. A number of technical replicates were included and are identified in the sample list. Insufficient muscle biopsy sample or inadequate RNA quality accounted for 8 missing data points (TechRep1 N=40 as opposed to 48).

Project description:The adult skeletal muscle is a plastic tissue with a remarkable ability to adapt to different levels of activity by altering its excitability, its contractile and metabolic phenotype and its mass. Knowledge on the mechanisms responsible for muscle mass comes primarily from models of muscle inactivity or denervation or from genetic models of muscle diseases. Given that the underlying exercise-induced transcriptional mechanisms regulating muscle mass are not fully understood, here we investigated the cellular and molecular adaptive mechanisms taking place in fast skeletal muscle of adult zebrafish in response to swimming. Fish were trained at low swimming speed (0.1 m/s; non-exercised) or at their optimal swimming speed (0.4 m/s; exercised). A significant increase in fibre cross-sectional area (1,290 M-BM-1 88 vs. 1,665 M-BM-1 106 M-NM-<m2) and vascularization (298 M-BM-1 23 vs. 458 M-BM-1 38 capillaries/mm2) was found in exercised over non-exercised fish. Gene expression profiling evidenced the transcriptional activation of a series of complex networks of extracellular and intracellular signaling molecules and pathways involved in the regulation of muscle mass, myogenesis and angiogenesis, many (e.g. BMP, TGFM-oM-^AM-", FGF, Notch, Wnt, MEF2, Shh, EphrinB2) not previously associated with exercise-induced contractile activity, and that recapitulate in part the transcriptional events occurring during skeletal muscle regeneration. These results demonstrate that fibre hypertrophy is responsible for the growth-promoting effects of exercise accompanied by a switch to a more oxidative capacity of white muscle fibres to fuel the increased energy demands. Importantly, our study identified novel molecular mechanisms regulating muscle mass and function in vertebrates. Adult zebrafish were subjected or not to a swim training regime consisting of swimming at the optimal swimming speed for this species for 6 h/day, 5 days/week for a total of 4 weeks (20 experimental days). Total RNA of fast muscle from individual non-exercised (n = 8) and exercised (n = 8) zebrafish was analyzed.

Dataset Information

Exercise sensitizes the pressure diuresis response: shifting immune landscapes underlie renal adaptations to exercise

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets