ArticleProceedings of the National Academy of Sciences of the United States of America2011
Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.Molecular biology of the cell · 2022Article
- Roles of Keratins in Intestine.International journal of molecular sciences · 2022Review
- Plectin ensures intestinal epithelial integrity and protects colon against colitis.Mucosal immunology · 2021Article
- αMolecular cancer research : MCR · 2019Article
- The role of keratins in the digestive system: lessons from transgenic mouse models.Histochemistry and cell biology · 2018Review
- Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-MediatedFrontiers in cellular and infection microbiology · 2018Article
- Keratin 8 reduces colonic permeability and maintains gut microbiota homeostasis, protecting against colitis and colitis-associated tumorigenesis.Oncotarget · 2017Article
- Article
- Intermediate Filaments and the Regulation of Cell Motility during Regeneration and Wound Healing.Cold Spring Harbor perspectives in biology · 2017Review
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Keratins regulate colonic epithelial cell differentiation through the Notch1 signalling pathway.Cell death and differentiation · 2017Article
- Article
- Review
- Review
- Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Absence of keratin 8 or 18 promotes antimitochondrial autoantibody formation in aging male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Keratin 8 absence down-regulates colonocyte HMGCS2 and modulates colonic ketogenesis and energy metabolism.Molecular biology of the cell · 2015Article
- Article
- Altered Protein Expression in the Ileum of Mice Associated with the Development of Chronic Infections with Echinostoma caproni (Trematoda).PLoS neglected tropical diseases · 2015Article
- Inflammation decreases keratin level in ulcerative colitis; inadequate restoration associates with increased risk of colitis-associated cancer.BMJ open gastroenterology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Keratin 8 (K8) is a major intermediate filament protein present in enterocytes and serves an antiapoptotic function in hepatocytes. K8-null mice develop colonic hyperplasia and colitis that are reversed after antibiotic treatment. To investigate the pathways that underlie the mechanism of colonocyte hyperplasia and the normalization of the colonic phenotype in response to antibiotics, we performed genome-wide microarray analysis. Functional annotation of genes that are differentially regulated in K8(-/-) and K8(+/+) isolated colon crypts (colonocytes) identified apoptosis as a major altered pathway. Exposure of K8(-/-) colonocytes or colon organ ("organoid") cultures, but not K8(-/-) small intestine organoid cultures, to apoptotic stimuli showed, surprisingly, that they are resistant to apoptosis compared with their wild-type counterparts. This resistance is not related to inflammation per se because T-cell receptor α-null (TCR-α(-/-)) and wild-type colon cultures respond similarly upon induction of apoptosis. Following antibiotic treatment, K8(-/-) colonocytes and organ cultures become less resistant to apoptosis and respond similarly to the wild-type colonocytes. Antibiotics also normalize most differentially up-regulated genes, including survivin and β4-integrin. Treatment of K8(-/-) mice with anti-β4-integrin antibody up-regulated survivin, and induced phosphorylation of focal adhesion kinase with decreased activation of caspases. Therefore, unlike the proapoptotic effect of K8 mutation or absence in hepatocytes, lack of K8 confers resistance to colonocyte apoptosis in a microflora-dependent manner.
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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.