biostudies-literatureStenvall CANIGMS NIH HHSar121https://www.ebi.ac.uk/biostudies/studies/S-EPMC9634972biostudies-literatureUnknown33(13)Keratin intermediate filaments convey mechanical stability and protection against stress to epithelial cells. Keratins are essential for colon health, as seen in keratin 8 knockout (K8^-/-) mice exhibiting a colitis phenotype. We hypothesized that keratins support the nuclear envelope and lamina in colonocytes. K8^-/- colonocytes in vivo exhibit significantly decreased levels of lamins A/C, B1, and B2 in a colon-specific and cell-intrinsic manner. CRISPR/Cas9- or siRNA-mediated K8 knockdown in Caco-2 cells similarly decreased lamin levels, which recovered after reexpression of K8 following siRNA treatment. Nuclear area was not decreased, and roundness was only marginally increased in cells without K8. Down-regulation of K8 in adult K8^flox/flox;Villin-CreER<suMolecular biology of the cellCytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.PMC9634972P01 GM096971Nystrom JHHeikkila TRHToivola DMJansson TFoisner RGoldman RDRidge KMButler-Hallissey CAdam SAStenvall CAfalseCytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.Keratin intermediate filaments convey mechanical stability and protection against stress to epithelial cells. Keratins are essential for colon health, as seen in keratin 8 knockout (K8^-/-) mice exhibiting a colitis phenotype. We hypothesized that keratins support the nuclear envelope and lamina in colonocytes. K8^-/- colonocytes in vivo exhibit significantly decreased levels of lamins A/C, B1, and B2 in a colon-specific and cell-intrinsic manner. CRISPR/Cas9- or siRNA-mediated K8 knockdown in Caco-2 cells similarly decreased lamin levels, which recovered after reexpression of K8 following siRNA treatment. Nuclear area was not decreased, and roundness was only marginally increased in cells without K8. Down-regulation of K8 in adult K8^flox/flox;Villin-CreER<su2022-01-01T00:00:00Z2022 Nov2025-04-21T14:17:03.948Z2025-04-21T14:17:03.948ZS-EPMC96349723600136510.1091/mbc.E20-06-0387