Partially differentiated ileal and distal-colonic human F508del-cystic fibrosis-enteroids secrete fluid in response to forskolin and linaclotide.

ABSTRACT: Constipation causes significant morbidity in patients with cystic fibrosis (CF). Using CF patient (F508del) derived ex vivo ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells. While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP), which was ∼48%, and ∼67% of the response in healthy enteroids, respectively, and was prevented by a CFTR inhibitor. Also, linac

SUBMITTER: Rong Y 

PROVIDER: S-EPMC12090326 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature