ArticleeLife2022
MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Doxorubicin induces ferroptosis in endometrial cancer by suppressing the MKK6/p38/CEBPB axis.Journal of translational medicine · 2026Article
- Immune regulation of Chidamide-induced Linc01010 accumulation in breast cancer cell death.World journal of clinical oncology · 2025Article
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.Experimental & molecular medicine · 2025Article
- Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner.Clinical science (London, England : 1979) · 2025Article
- The mTOR Signaling Pathway: Key Regulator and Therapeutic Target for Heart Disease.Biomedicines · 2025Review
- Map2k6 is a potent genetic modifier of arterial rupture in vascular Ehlers-Danlos syndrome mice.JCI insight · 2025Article
- Galactin-8 DNA methylation mediates macrophage autophagy through the MAPK/mTOR pathway to alleviate atherosclerosis.Scientific reports · 2025Article
- Fibroblast Growth Factor 21 Promotes Vascular Smooth Muscle Cell Contractile Polarization via p38 Mitogen-Activated Protein Kinase-Promoted Serum Response Factor Phosphorylation.Research (Washington, D.C.) · 2025Article
- The intersection ofFrontiers in cellular and infection microbiology · 2025Review
- Chinese medicine in the treatment of chronic hepatitis B: The mechanisms of signal pathway regulation.Heliyon · 2024Review
- Remodeling p38 signaling in muscle controls locomotor activity via IL-15.Science advances · 2024Article
- Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.Genome medicine · 2024Article
- MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.Science advances · 2024Article
- p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.Nature cardiovascular research · 2023Article
- Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality.JACC. Heart failure · 2023Article
- Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model.Frontiers in immunology · 2023Article
- TheScience signaling · 2022Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Stress-activated p38 kinases control a plethora of functions, and their dysregulation has been linked to the development of steatosis, obesity, immune disorders, and cancer. Therefore, they have been identified as potential targets for novel therapeutic strategies. There are four p38 family members (p38α, p38β, p38γ, and p38δ) that are activated by MKK3 and MKK6. Here, we demonstrate that lack of MKK6 reduces the lifespan in mice. Longitudinal study of cardiac function in MKK6 KO mice showed that young mice develop cardiac hypertrophy which progresses to cardiac dilatation and fibrosis with age. Mechanistically, lack of MKK6 blunts p38α activation while causing MKK3-p38γ/δ hyperphosphorylation and increased mammalian target of rapamycin (mTOR) signaling, resulting in cardiac hypertrophy. Cardiac hypertrophy in MKK6 KO mice is reverted by knocking out either p38γ or p38δ or by inhibiting the mTOR pathway with rapamycin. In conclusion, we have identified a key role for the MKK3/6-p38γ/δ pathway in the development of cardiac hypertrophy, which has important implications for the clinical use of p38α inhibitors in the long-term treatment since they might result in cardiotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.