Severe downregulation of the NHE3 adapterprotein PDZK1 (NHERF3) in colonic mucosa of patients with active IBD – Implications for the dysregulation of salt and water transport

Aims: Acute flares of UC (ulcerative colitis) an CD (Crohn's disease) are often accompanied by severe diarrhea. A major causative factor is the complete loss of sodium absorptive capacity of the inflamed colonic mucosa of patients with acute UC or CD. Intestinal cell lines incubated with TNFα and IFNγ showed downregulation of the major transport protein for intestinal salt absorption, the Na+/H+ exchanger isoform 3 (NHE3) mRNA expression, but surprisingly, we did not find this in the colon of mouse models for IBD. We found, however, a severe downregulation of the NHE3 adapter protein PDZK1 (NHERF3), which is a m…