Researchers have linked two genes to inflammatory bowel disease (IBD).
Now, Cincinnati Cancer Center and University of Cincinnati (UC) Cancer Institute researcher Susan Waltz, PhD, and scientists in her lab have done what is believed to be the first direct genetic study to document the important function for the Ron receptor, a cell surface protein often found in certain cancers, and its genetic growth factor, responsible for stimulating cell growth, in the development and progression of IBD.
Waltz, professor in the department of cancer biology at UC, said genome-wide linkage studies have identified the Ron receptor tyrosine kinase and its hepatocyte growth factor-like protein (HGFL) as genes highly associated with IBD, asserting that only scant information exists on the role of Ron or HGFL in IBD. Based on the linkage of Ron to IBD, they examined the biological role of Ron in colitis - swelling of the large intestine (colon).
In the study, Waltz and Rishikesh Kulkarni, PhD, a postdoctoral fellow in UC's department of cancer biology, used animal models with colitis. A genetic knockout group did not have Ron; the other did.
"We found that genetic loss of Ron led to aggressive inflammation and damage to the colon of models with IBD," she says.
Loss of Ron also led to significantly reduced body weight and a dramatic reduction in colon tissue cell growth as well as increased pro-inflammatory cytokine (proteins important in cell signaling) production, which was associated with changes in important signaling pathways known to regulate IBD.
The results have been published online in the American Journal of Physiology-Gastrointestinal and Liver Physiology.
