CITED4 is Required for Exercise-induced Cardiac Growth and Cardiomyogenesis in Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE228969 | GEO | 2025/04/03
REPOSITORIES: GEO
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Project description:Rationale: Cardiac CITED4 is induced by exercise and is sufficient to cause physiological hypertrophy and mitigate adverse ventricular remodeling after ischemic injury. However, the role of endogenous CITED4 in response to physiological or pathological stress is unknown. Objective: To investigate the role of CITED4 in murine models of exercise and pressure overload. Methods and Results: We generated cardiomyocyte-specific CITED4 knockout mice (C4KO) and subjected them to an intensive swim exercise protocol as well as transverse aortic constriction (TAC). Echocardiography, western blotting, qPCR, immunohistochemistry, immunofluorescence, and transcriptional profiling for mRNA and miRNA expression were performed. Cellular crosstalk was investigated in vitro. CITED4 deletion in cardiomyocytes did not affect baseline cardiac size or function in young adult mice. C4KO mice developed modest cardiac dysfunction and dilation in response to exercise. After TAC, C4KOs developed severe heart failure with left ventricular dilation, impaired cardiomyocyte growth accompanied by reduced mammalian target of rapamycin (mTOR) activity and maladaptive cardiac remodeling with increased apoptosis, autophagy, and impaired mitochondrial signaling. Interstitial fibrosis was markedly increased in C4KO hearts after TAC. RNAseq revealed induction of a pro-fibrotic miRNA network. miR30d was decreased in C4KO hearts after TAC and mediated crosstalk between cardiomyocytes and fibroblasts to modulate fibrosis. miR30d inhibition was sufficient to increase cardiac dysfunction and fibrosis after TAC. Conclusions: CITED4 protects against pathological cardiac remodeling by regulating mTOR activity and a network of miRNAs mediating cardiomyocyte to fibroblast crosstalk. Our findings highlight the importance of CITED4 in response to both physiological and pathological stimuli.
2020-04-30 | GSE149584 | GEO
Project description:CITED4 is Required for Exercise-induced Cardiac Growth and Cardiomyogenesis in Mice
| PRJNA952256 | ENA
Project description:Transcriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or M-bM-^@M-^\exercise ancestry,M-bM-^@M-^] on morphological and metabolic phenotypes in multiple generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bred with like-exposed mates to produce an F1 generation. F1 mice of both ancestries were sedentary and sacrificed at 8 wk or bred with littermates to produce an F2 generation, which was also sedentary and sacrificed at 8 wk. Small, but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance, and muscle gene expression. F1 EX females were heavier than F1 SED females, but F1 SED females had higher absolute tibialis anterior and omental fat masses. Serum insulin was lower in F1 SED females compared to F1 EX females. F2 EX females had impaired glucose tolerance compared to F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g., F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1M-NM-1, Adipoq, and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring. We analyzed RNA from 10 males each from exercise and sedentary ancestries over 2 generations of offspring (F1 and F2)
2012-08-30 | E-GEOD-40469 | biostudies-arrayexpress
Project description:Gene profiling hippocampal mRNA from 1 week sedentary mice vs. 1 week voluntary exercise mice. Keywords: Exercise study.
2007-11-30 | GSE9565 | GEO
Project description:In order to assess the impact of treadmill exercise on traumatic brain injury outcomes, we subjected male and female swiss webster mice to a controlled cortical impact (CCI), followed by 10 days of sedentary, low-, moderate-, or high-intensity treadmill exercise. Outcome measures included neurometabolic function, cognitive recovery, oxidative stress, pathophysiology, and single nuclei RNA sequencing (snRNA seq). The snRNA seq study was conducted on both male and female mice, and included a total of 2 replicates (each was a pool of 2 tissue samples) from each of the following groups: male sham sedentary, male CCI sedentary, male CCI low, male CCI high, female sham sedentary, female CCI sedentary, female CCI low, female CCI high. Our data reveal exercise intensity- and sex-dependent effects of treadmill exercise following injury. Transcriptomic changes were largely limited to the low-intensity exercised CCI males.
2023-08-01 | GSE226072 | GEO
Project description:Transcriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or “exercise ancestry,” on morphological and metabolic phenotypes in multiple generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bred with like-exposed mates to produce an F1 generation. F1 mice of both ancestries were sedentary and sacrificed at 8 wk or bred with littermates to produce an F2 generation, which was also sedentary and sacrificed at 8 wk. Small, but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance, and muscle gene expression. F1 EX females were heavier than F1 SED females, but F1 SED females had higher absolute tibialis anterior and omental fat masses. Serum insulin was lower in F1 SED females compared to F1 EX females. F2 EX females had impaired glucose tolerance compared to F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g., F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1α, Adipoq, and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring.
2012-08-30 | GSE40469 | GEO
Project description:Gene expression and phenotypic consequences of laboratory housing in rats. Disease related-phenotypes and associated gene expressions of sedentary animals (living solely in a standard cage) were compared with animals that had access to twice-weekly one-hour physical activity in a large box (PA) and with those that had access to voluntary running wheel exercise (EX). Keywords: exercise dose reponse, sedentary, twice weekly physical activity, daily exercise
2006-07-01 | GSE5085 | GEO
Project description:Consequence of physical exercise in skeletal muscle was investigated in C57BL/6 mice after 4 weeks of exercise training and compared to sedentary controls. Exercised mice received four 4 weeks of regular exercise training on a motorized treadmill and were compared to sedentary controls. 6 mice of each Treatment were used to extract RNA from the quadriceps muscle three hours after the last training bout
2015-02-01 | E-GEOD-54276 | biostudies-arrayexpress
Project description:Analysis of heart from myocardil specific deletion of Jarid2 by crossing Jarid2 floxed mice with aMHC-Cre mice (Jarid2-aMHC). Jarid2-aMHC mice regult in dilated cardomyopathy and reveal premature death. To identify differentially expressed genes in Jarid2-aMHC hearts, we performed RNA-seq analysis on mutant hearts and control heart at postnatal day 10 (P10) and 7 months of ages (7M).
2018-08-23 | GSE118945 | GEO
Project description:Seventy two rats were randomized to twelve independent groups of rats (n = 6 in all groups) where half of the rats were chosen for training (treadmill exercise training 1.5 hour 5 days a week, in 1, 4, 24, 48 days and for 4 and 8 weeks) or sedentary (no training) as described in detail by Wisloff et al. (Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1301-10.) or Kemi et al.(Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation. 2004 Jun 15;109(23):2897-904. Epub 2004 Jun 1.). The rats were scarified one hour after training (1, 4, 24 and 48 days) or 24 hours after training (4 and 8 weeks). Biopsies form left ventricle was taken form all rats and stored on -80°C for preparation of RNA. The same procedures were performed for the control/sedentary rats which were sacrificed at the same time as the exercised rats.
2006-11-10 | E-TABM-166 | biostudies-arrayexpress