ArticleCell death & disease2018
Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Trial
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- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- LINCRNA01094 Promotes Renal Interstitial Fibrosis via the Mir-513b-5p/ MELK/Smad3 Axis.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Navigating the Maze of Kinases: CaMK-like Family Protein Kinases and Their Role in Atherosclerosis.International journal of molecular sciences · 2024Review
- MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function.Cell death & disease · 2023Article
- Excavation and characterization of key circRNAs for milk fat percentage in Holstein cattle.Journal of animal science · 2023Article
- Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease.Biomolecules · 2022Article
- Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions.International journal of molecular sciences · 2022Article
- Transcriptome-wide analyses of adipose tissue in outbred rats reveal genetic regulatory mechanisms relevant for human obesity.Physiological genomics · 2022Article
- Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants.Journal of the National Cancer Institute · 2021Article
- Genomic Analysis of Visceral Fat Accumulation in Holstein Cows.Frontiers in genetics · 2021Article
- TGF-β: The missing link in obesity-associated airway diseases?Current research in pharmacology and drug discovery · 2021Review
- Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome.Frontiers in endocrinology · 2021Article
- Overexpression of Smad7 in hypothalamic POMC neurons disrupts glucose balance by attenuating central insulin signaling.Molecular metabolism · 2020Article
- Iron Metabolism in Obesity and Metabolic Syndrome.International journal of molecular sciences · 2020Review
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Authors and funding
3 authors.
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Abstract
Smad proteins have been implicated in metabolic processes, but little is known about how they regulate metabolism. Because Smad 2, 3, 4, and 7 have previously been shown to interact with murine protein serine-threonine kinase 38 (MPK38), an AMP-activated protein kinase (AMPK)-related kinase that has been implicated in obesity-associated metabolic defects, we investigated whether Smad proteins regulate metabolic processes via MPK38. Smads2/3/4 increased, but Smad7 decreased, MPK38-mediated apoptosis signal-regulating kinase-1 (ASK1)/transforming growth factor-β (TGF-β)/p53 signaling. However, MPK38-mediated phosphorylation-defective Smad mutants (Smad2 S245A, Smad3 S204A, Smad4 S343A, and Smad7 T96A) had no such effect. In addition, Smads2/3/4 increased, but Smad7 decreased, the stability of MPK38. Consistent with this, Smads2/3/4 attenuated complex formation between MPK38 and its negative regulator thioredoxin (Trx), whereas Smad7 increased this complex formation. However, an opposite effect was observed on complex formation between MPK38 and its positive regulator zinc-finger-like protein 9 (ZPR9). When Smads were overexpressed in high-fat diet (HFD)-fed obese mice using an adenoviral delivery system, Smads2/3/4 improved, but Smad7 worsened, obesity-associated metabolic parameters and inflammation in a MPK38 phosphorylation-dependent manner. These findings suggest that Smad proteins have class-specific impacts on obesity-associated metabolism by differentially regulating MPK38 activity in diet-induced obese mice.
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