CINCINNATI—Inflammatory Bowel Disease (IBD),
a group of chronic inflammatory disorders of the intestine that result in
painful and debilitating complications, affects over 1.4 million people in the
U.S., and while there are treatments to reduce inflammation for patients, there
is no cure.
Now, Cincinnati Cancer Center and University
of Cincinnati 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.
These results are published in the advance
online edition of the American Journal of Physiology-Gastrointestinal and
"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,” says Waltz, professor in the
department of cancer biology at UC. "However, only scant information exists on
the role of Ron or HGFL in IBD. Based on the linkage of Ron to IBD, we examined
the biological role of Ron in colitis.”
Colitis is swelling of the large intestine
(colon) and is a potentially pre-cancerous condition.
Waltz says that due to her lab’s
cancer-related expertise with studying Ron and HGFL, she and her colleagues had
all of the tools to translate their knowledge of the study of these proteins in
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.
"In addition, there are a number of small
changes called single nucleotide polymorphisms (SNP) in humans which map to
both the Ron and HGFL gene and have been identified to strongly associate IBD
disease in humans,” Waltz says. "Our studies suggest that these SNPs may reduce
the function of Ron and HGFL leading to chronic intestinal inflammation and
"With the knowledge that we’ve gained in
studying these proteins in cancer biology, we hope this information may be
translated to help patients with Crohn’s disease and ulcerative colitis.
Further studies on the Ron signaling pathway are needed and could reveal an
important new target for these conditions.”
This study was funded in part by Public
Health Services (CA125379), a National Institutes of Health P30 (DK078392)
grant, the U.S. Veterans Administration (VA1001BX000803) and the American Heart
Association Great Rivers Affiliates (12POST12040055). Researchers involved in
the study include Waltz, Kulkarni, Devi Gurusamy, PhD, and William Stuart.
Waltz cites no conflict of interest.
The University of Cincinnati, Cincinnati Children’s Hospital Medical Center and
UC Health have created the Cincinnati Cancer Center—a joint effort designed to
leverage the strengths of all three organizations in order to provide the best
possible cancer diagnostics, research, treatment, and care for individuals in
the Tristate region and the nation. To learn more, visit cincinnaticancercenter.org.