ArticleNature communications2022
Kindlin-2 haploinsufficiency protects against fatty liver by targeting Foxo1 in mice.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
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- Sustained Hypoxia-Inducible Factor 1-Alpha Accumulation Disrupts the Articular Niche to Promote Osteoarthritis Pathogenesis.Aging cell · 2026Article
- PROTAC-mediated PCSK9 degradation attenuates atherosclerosis and improves plaque composition via suppression of NF-κB/TNF-α pathway.BMC medicine · 2026Article
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- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Liquiritin restores metabolic homeostasis in NAFLD by modulating AKT1/FOXO1 signaling.Frontiers in pharmacology · 2026Article
- IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating FOXP1 SUMOylation.International journal of biological sciences · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- The Sirt1-Piezo1 Axis Promotes Bone Formation and Repair in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice.Bone research · 2025Article
- Chaperone-mediated autophagy manipulates PGC1α stability and governs energy metabolism under thermal stress.Nature communications · 2025Article
- Targeting Piezo1 channel to alleviate intervertebral disc degeneration.Journal of orthopaedic translation · 2025Article
- Enhancing the Therapeutic Efficacy of Berberine and Quercetin Through Salt Formulation for Liver Fibrosis Treatment.International journal of molecular sciences · 2025Article
- The p53-miR17 family-Rankl axis bridges liver-bone communication.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The effect of disulfidptosis induced by glucose starvation in SLC7A11Frontiers in cell and developmental biology · 2025Article
- Article
- The role of ubiquitination and deubiquitination in the pathogenesis of non-alcoholic fatty liver disease.Frontiers in immunology · 2025Review
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects a large population with incompletely defined mechanism(s). Here we report that Kindlin-2 is dramatically up-regulated in livers in obese mice and patients with NAFLD. Kindlin-2 haploinsufficiency in hepatocytes ameliorates high-fat diet (HFD)-induced NAFLD and glucose intolerance without affecting energy metabolism in mice. In contrast, Kindlin-2 overexpression in liver exacerbates NAFLD and promotes lipid metabolism disorder and inflammation in hepatocytes. A C-terminal region (aa 570-680) of Kindlin-2 binds to and stabilizes Foxo1 by inhibiting its ubiquitination and degradation through the Skp2 E3 ligase. Kindlin-2 deficiency increases Foxo1 phosphorylation at Ser256, which favors its ubiquitination by Skp2. Thus, Kindllin-2 loss down-regulates Foxo1 protein in hepatocytes. Foxo1 overexpression in liver abrogates the ameliorating effect of Kindlin-2 haploinsufficiency on NAFLD in mice. Finally, AAV8-mediated shRNA knockdown of Kindlin-2 in liver alleviates NAFLD in obese mice. Collectively, we demonstrate that Kindlin-2 insufficiency protects against fatty liver by promoting Foxo1 degradation.
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