Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.

ABSTRACT: 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

SUBMITTER: Stenvall CA 

PROVIDER: S-EPMC9634972 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature