ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Trichinella spiralis serine protease mediates larval invasion of gut epithelium via binding to CK8 and activating RhoA/ROCK1 pathway.PLoS neglected tropical diseases · 2025Article
- Colonocyte keratins stabilize mitochondria and contribute to mitochondrial energy metabolism.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Detection of Intestinal Inflammation by Vascular Adhesion Protein-1-Targeted [Molecular imaging and biology · 2024Article
- Defining a timeline of colon pathologies after keratin 8 loss: rapid crypt elongation and diarrhea are followed by epithelial erosion and cell exfoliation.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.Molecular biology of the cell · 2022Article
- Identification of a Novel Link between the Intermediate Filament Organizer IFO-1 and Cholesterol Metabolism in theInternational journal of molecular sciences · 2020Article
- Knockdown of cytokeratin 8 overcomes chemoresistance of chordoma cells by aggravating endoplasmic reticulum stress through PERK/eIF2α arm of unfolded protein response and blocking autophagy.Cell death & disease · 2019Article
- Clostridium difficile toxins A and B decrease intestinal SLC26A3 protein expression.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-MediatedFrontiers in cellular and infection microbiology · 2018Article
- Activation of Nuclear Factor-κB by Tumor Necrosis Factor in Intestinal Epithelial Cells and Mouse Intestinal Epithelia Reduces Expression of the Chloride Transporter SLC26A3.Gastroenterology · 2017Article
- Keratins regulate colonic epithelial cell differentiation through the Notch1 signalling pathway.Cell death and differentiation · 2017Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Keratins (K) are intermediate filament proteins important in protection from stress. The roles of keratins in the intestine are not clear, but K8 knockout (K8(-/-)) mice develop a Th2-type colonic inflammation, epithelial hyperproliferation, and mild diarrhea caused by a keratin level-dependent decrease in short-circuit current and net sodium and chloride absorption in the distal colon. The lack of K8 leads to mistargeting or altered levels of membrane proteins in colonocytes; however, the main transporter responsible for the keratin-related ion transport defect is unknown. We here analyzed protein and mRNA levels of candidate ion transporters CFTR, PAT-1, NHE-3, and DRA in ileum, cecum, and proximal and distal colon. Although no differences were observed for CFTR, PAT-1, or NHE-3, DRA mRNA levels were decreased by three- to fourfold and DRA protein was almost entirely lost in K8(-/-) cecum and proximal and distal colon compared with K8(+/+), whereas the levels in ileum were normal. In K8(+/-) mice, DRA mRNA levels were unaltered, while decreased DRA protein levels were detected in the proximal colon. Immunofluorescence staining confirmed the loss of DRA in K8(-/-) distal colon, while K8(+/-) displayed a similar but more patchy apical DRA distribution compared with K8(+/+) DRA was similarly decreased when K8 was knocked down in Caco-2 cells, confirming that K8 levels modulate DRA levels in an inflammation-independent manner. Taken together, the loss of DRA in the K8(-/-) mouse colon and cecum explains the dramatic chloride transport defect and diarrheal phenotype after K8 inactivation and identifies K8 as a novel regulator of DRA.
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