TAK1 is essential for growth and maintenance of skeletal muscle mass
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ABSTRACT:
PROVIDER: PRJNA413137 | ENA |
REPOSITORIES: ENA
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Project description:Our results demonstrate that targeted deletion of TAK1 inhibits muscle growth during post-natal development period. Inactivation of TAK1 also causes muscle wasting in adult mice. TAK1 regulates expression of a number of molecules and signaling pathways which mediate growth and maintenance of skeletal muscle.
2018-02-28 | GSE104586 | GEO
Project description:In this study, we show that muscle-specific inactivation of FBXW7 elicits striking defects in postprandial glucose metabolism and failure to maintain skeletal muscle mass in adult mice. Further, mice lacking FBXW7 exhibited impaired endurance capacity and exacerbated HFD-induced insulin resistance and postprandial hyperglycemia. At the mechanistic level, RNAseq and quantitative proteomic analysis revealed global effects of FBXW7 deficiency on skeletal muscle transcriptome and proteome. This work illustrates a prominent role of FBXW7 in integrating postprandial nutritional signals to coordinate glucose metabolism and muscle mass maintenance.
2024-06-21 | GSE140503 | GEO
Project description:Negative regulation of immunoreceptor signaling is required for preventing hyperimmune activation and maintaining immune homeostasis. The roles of p38IP in immunoreceptor signaling remain unclear. Here, we show that p38IP suppresses T cell receptor (TCR)/LPS-activated NF-κB and p38 by targeting TAK1 kinase and that p38IP protein levels are downregulated in human-PBMCs from rheumatoid arthritis (RA) patients, inversely correlating with the enhanced activity of NF-κB and p38. Mechanistically, p38IP interacts with TAK1 to disassemble the TAK1-TAB (TAK1-binding protein) complex. p38IP overexpression decreases TCR-induced binding of K63-linked polyubiquitin (polyUb) chains to TAK1 but increases that to TAB2, and p38IP knockdown shows the opposite effects, indicating unanchored K63-linked polyUb chain transfer from TAB2 to TAK1. p38IP dynamically interacts with TAK1 upon stimulation, because of the higher binding affinity of TAK1 and p38IP for sequential polyUb binding by TAB2 and TAK1, respectively. Moreover, p38IP specifically scaffolds the deubiquitinase USP4 to deubiquitinate TAK1 once TAK1 is activated. These findings reveal a novel role and the mechanisms of p38IP in controlling TCR/LPS signaling and suggest that p38IP might participate in RA pathogenesis.
2020-04-30 | PXD018330 | Pride
Project description:Homeostatic control of dendritic cell (DC) survival is crucial for a productive adaptive immune response, but the molecular mechanism is not well defined. Moreover, how DCs influence homeostasis of the immune system under steady state remains unclear. Combining DC-specific and inducible deletion systems, we report here that the kinase TAK1 is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c+ cells diminished DC populations, especially the CD8+ and CD103+ DC subsets in the lymphoid and non-lymphoid organs, respectively. This was associated with increased apoptosis of DCs, whereas DC proliferation and differentiation from precursors appeared largely normal. In addition, acute deletion of TAK1 caused DC apoptosis, indicating a direct role of TAK1 in actively maintaining DC survival. TAK1 deficiency impaired activities of the pro-survival NF-kB and AKT pathways but upregulated expression of the pro-apoptotic molecule Bim. Under steady state, loss of TAK1 in DCs resulted in a myeloid proliferative disorder, and altered homeostasis of T cells. In response to antigen stimulation, TAK1-deficient DCs were impaired for T cell priming and regulatory T cell generation. Therefore, TAK1 orchestrates a pro-survival checkpoint in DCs that affects the homeostasis and function of the immune system RNA extracted from three replicate samples of wild-type and Map3k7 (TAK1) knockout dendritic cells was analyzed on Affymetrix gene expression arrays
2012-01-23 | E-GEOD-34417 | biostudies-arrayexpress
Project description:Homeostatic control of dendritic cell (DC) survival is crucial for a productive adaptive immune response, but the molecular mechanism is not well defined. Moreover, how DCs influence homeostasis of the immune system under steady state remains unclear. Combining DC-specific and inducible deletion systems, we report here that the kinase TAK1 is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c+ cells diminished DC populations, especially the CD8+ and CD103+ DC subsets in the lymphoid and non-lymphoid organs, respectively. This was associated with increased apoptosis of DCs, whereas DC proliferation and differentiation from precursors appeared largely normal. In addition, acute deletion of TAK1 caused DC apoptosis, indicating a direct role of TAK1 in actively maintaining DC survival. TAK1 deficiency impaired activities of the pro-survival NF-kB and AKT pathways but upregulated expression of the pro-apoptotic molecule Bim. Under steady state, loss of TAK1 in DCs resulted in a myeloid proliferative disorder, and altered homeostasis of T cells. In response to antigen stimulation, TAK1-deficient DCs were impaired for T cell priming and regulatory T cell generation. Therefore, TAK1 orchestrates a pro-survival checkpoint in DCs that affects the homeostasis and function of the immune system
2012-01-23 | GSE34417 | GEO
Project description:We propose that the Muscle-Brain-Gut axis regulates skeletal muscle mass through the defined mechanism.
2023-12-11 | GSE249324 | GEO
Project description:We propose that the Muscle-Brain-Gut axis regulates skeletal muscle mass through the defined mechanism.
2023-12-13 | GSE249515 | GEO
Project description:The vitamin D receptor (VDR) autonomously regulates skeletal muscle mass
| PRJNA433878 | ENA
Project description:Vitamin D (VitD) deficiency is estimated to affect ~40% of the world’s population. Notably, VitD deficiency has been associated with impaired muscle maintenance and insulin resistance. VitD exerts its actions through the ubiquitous Vitamin D-receptor (VDR), the expression of which was recently confirmed in fully-differentiated muscle. To seek a possible autonomous role of the VDR in skeletal muscle, we first generated stable VDR-knockdown cells, which exhibited impaired myogenesis (i.e. cell-cycling, differentiation and myotube formation). In vivo VDR-knockdown in rat hind-limbs elicited myofibre atrophy and triggered autophagy pathways. In contrast, in vivo VDR-overexpression yielded myofibre hypertrophy; enhancing translational efficiency (e.g. mTOR-signaling), ribosomal biogenesis and satellite cell content. Neither VDR-knockdown nor overexpression impacted muscle glucose uptake. Crucially, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise training, but not aspects of insulin sensitivity. The VDR autonomously regulates muscle mass, acting reciprocally to limit atrophy and promote hypertrophy.
2020-09-29 | GSE110507 | GEO
Project description:Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-?-activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism.
| S-EPMC5821216 | biostudies-literature