ArticleMolecular biology of the cell2015
Keratin 8 absence down-regulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Trial
- Regulation of Keratin Chemical Modifications: Potential Molecular Mechanisms in Proliferative Diseases.International journal of molecular sciences · 2026Review
- Ketone ester supplementation protects from experimental colitis via improved goblet cell differentiation and function.European journal of nutrition · 2025Article
- Trichinella spiralis serine protease mediates larval invasion of gut epithelium via binding to CK8 and activating RhoA/ROCK1 pathway.PLoS neglected tropical diseases · 2025Article
- Searching for protein partners of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) reveals keratin 8 as a novel candidate for interaction in pancreatic β-cells.BMC molecular and cell biology · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Colonocyte keratins stabilize mitochondria and contribute to mitochondrial energy metabolism.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Article
- Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice.The Biochemical journal · 2024Article
- The apoptotic effects of soybean agglutinin were induced through three different signal pathways by down-regulating cytoskeleton proteins in IPEC-J2 cells.Scientific reports · 2023Article
- Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.Frontiers in immunology · 2023Article
- Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.Molecular biology of the cell · 2022Article
- Dietary selection of metabolically distinct microorganisms drives hydrogen metabolism in ruminants.The ISME journal · 2022Article
- Targeted deletion of keratin 8 in intestinal epithelial cells disrupts tissue integrity and predisposes to tumorigenesis in the colon.Cellular and molecular life sciences : CMLS · 2021Article
- Ketogenic Diet as a potential treatment for traumatic brain injury in mice.Scientific reports · 2021Article
- An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps.International journal of molecular sciences · 2020Review
- Resistin Activates p65 Pathway and Reduces Glycogen Content through Keratin 8.International journal of endocrinology · 2020Article
- Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins.F1000Research · 2019Review
- The role of keratins in the digestive system: lessons from transgenic mouse models.Histochemistry and cell biology · 2018Review
- Comparative proteomic analysis of rats subjected to water immersion and restraint stress as an insight into gastric ulcers.Molecular medicine reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Simple-type epithelial keratins are intermediate filament proteins important for mechanical stability and stress protection. Keratin mutations predispose to human liver disorders, whereas their roles in intestinal diseases are unclear. Absence of keratin 8 (K8) in mice leads to colitis, decreased Na/Cl uptake, protein mistargeting, and longer crypts, suggesting that keratins contribute to intestinal homeostasis. We describe the rate-limiting enzyme of the ketogenic energy metabolism pathway, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), as a major down-regulated protein in the K8-knockout (K8(-/-)) colon. K8 absence leads to decreased quantity and activity of HMGCS2, and the down-regulation is not dependent on the inflammatory state, since HMGCS2 is not decreased in dextran sulfate sodium-induced colitis. Peroxisome proliferator-activated receptor α, a transcriptional activator of HMGCS2, is similarly down-regulated. Ketogenic conditions-starvation or ketogenic diet-increase K8(+/+) HMGCS2, whereas this response is blunted in the K8(-/-) colon. Microbiota-produced short-chain fatty acids (SCFAs), substrates in the colonic ketone body pathway, are increased in stool, which correlates with decreased levels of their main transporter, monocarboxylate transporter 1 (MCT1). Microbial populations, including the main SCFA-butyrate producers in the colon, were not altered in the K8(-/-). In summary, the regulation of the SCFA-MCT1-HMGCS2 axis is disrupted in K8(-/-) colonocytes, suggesting a role for keratins in colonocyte energy metabolism and homeostasis.
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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.