PUMA-mediated intestinal apoptosis contributes to ulcerative colitis in humans, mice

Ulcerative colitis (UC) is an inflammatory bowel disease thought to be related to aberrant activation of the immune system in the intestine. Recent research has also suggested that regulated cell death (apoptosis) of the intestinal epithelial cells is a contributing factor to the pathogenesis. However, the molecular mechanisms that control the cellular response to inflammation are incompletely understood.

In this paper, Lin Zhang, at the University of Pittsburgh, in Pennsylvania, found that in mice, a protein called PUMA (p53 upregulated modulator of apoptosis) was responsible for inducing apoptosis in the intestinal epithelium in response to inflammation; the absence of PUMA inhibited the inflammation-induced death of intestinal epithelial cells and development of colitis. PUMA levels were also increased in the diseased tissues of UC patients. The researchers are hopeful that PUMA could represent a promising target for the development of new UC therapies.

Source: Journal of Clinical Investigation