Semester

Summer

Date of Graduation

2019

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Robert Brock

Committee Co-Chair

V.M. Rajendran

Committee Member

V.M. Rajendran

Committee Member

Justin Kupec

Committee Member

Eric Kelley

Committee Member

David Siderovski

Abstract

Though the duodenum is the primary site of iron absorption, the colon also contains iron transporters and participates in iron absorption. The purpose of this study was to characterize colonic iron absorption in control patients and those with ulcerative colitis (UC), a disease that frequently results in iron deficiency. Using RT-qPCR and western blot analysis, we found that colonic expression of the apical iron importer, divalent metal transporter 1 (DMT1), is equal to duodenal expression. However, colonic expression of ferroportin 1 (FPN1), an iron exporter, is only about one-quarter that of the duodenum. Patients with active ulcerative colitis were found to have increased DMT1 (2x) and FPN1 (5X) in the colon. Immunostaining demonstrated that the transporters were localized to membrane (DMT1-apical, FPN1-basolateral) and 59Fe uptake studies revealed that the transporters contributed to increased colonic iron uptake in UC tissue, which may help alleviate the iron deficiency that is a frequent complication of UC.

Once we identified the colon as an ideal site to target for iron absorption in ulcerative colitis, we next wanted to determine whether it is safe to prescribe oral iron supplementation to patients with UC. Using an animal model of colitis, we found that oral iron supplementation led to increased disease activity. However, we cannot make any definitive conclusions without conducing a human clinical trial. If we find that colonic iron absorption is not a suitable treatment in UC then we can pursue it for other causes of iron deficiency, such as Celiac disease or gastric bypass.

Download

Share

COinS