Lrig3 is Required for Colonic Regeneration Following Acute Inflammatory Injury

Presenter: Kevin Mueller – Biology

Faculty Mentor(s): Anne Zemper, Janelle Stevenson

Session: (In-Person) Oral Panel—Daily Dose of Proteins

The mouse colon is a tightly regulated organ responsible for secreting mucus and absorbing water, which is carried out by colonic crypts; small U-shaped invaginations in the colon’s epithelial tissue. The excision of the protein Lrig3 has been characterized in homeostasis and is defined by more nuclei per crypt, increased mucosal area, and an expanded stem cell compartment consisting of more Lrig1+ cells per crypt. While we now understand that Lrig3 plays an important role in homeostasis, it is currently unknown what role Lrig3 might play in colon-based diseases. The disease we chose to test first was the mouse model of ulcerative colitis. Our lab treated two cohorts of mice, one Wild Type (WT) and one Lrig3-/-, with a 3% Dextran Sodium Sulfate (DSS) solution over 6 days to induce inflammation. Both cohorts were allowed to recover for 24 hours before analysis. We found Lrig3-/-mice are more susceptible to DSS treatment and lack the colonic regenerative capability seen in WT mice. We then performed immunohistochemistry, dye, and enzymatic-based analyses to examine the expression profiles of proteins associated with regeneration of the colonic epithelium. We observed a decrease in cells expressing the stem and progenitor marker Lrig1 in Lrig3-/- mice compared to WT (p<0.01) and a decrease in the total cell number per crypt (p<0.001), however there was no change in proliferation. These data suggest Lrig3 is required for epithelial regeneration in DSS- modeled ulcerative colitis.

Exploring the Role of Lrig3 In the Colon

Presenter(s): Ryan Sayegh

Faculty Mentor(s): Annie Zemper & Janelle Stevenson

Poster 9

Session: Sciences

The colon is a vital organ for digestion. Its inner epithelial lining has tubular invaginations known as colonic crypts. These crypts contribute to a dynamic system containing stem cells necessary for colonic repair and maintenance (Barker et al. 2014). Disruption of the colonic crypt system is a symptom of diseases like Irritable Bowel Disease, colitis, and colorectal cancer. The protein EGFR plays an important role in the cell proliferation necessary for maintaining homeostasis within the colon. Leucine-rich repeats and immunoglobulin like domains 1 (Lrig1) is a protein that plays an antagonizing role to Egfr (Wang et al. 2013). LRIG3, a homolog of LRIG1 was shown to positively regulate EGFR in a cell culture model (Rafidi et al. 2013). However, its role in the colon remains unknown. I hypothesize that mice lacking Lrig3 (Lrig3-/-) will have smaller epithelial tissue areas with lower expression of Egfr. I used immunofluorescence to analyze the expression of Egfr in the absence of Lrig3 and found no difference compared to control mice. I then analyzed colonic epithelial area using Hematoxylin and Eosin staining and found that Lrig3- /- mice had a larger area of epithelial tissue when compared to control mice. These data show that Lrig3 may be playing a different role in the Egfr pathway than what other models would suggest.