Change in the Gastro-Intestinal Tract by Overexpressed Activin Beta A

Abstract

Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin beta(A) on the body, including the gastro-intestinal (GI) tract. Initially, the activin beta(A) protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin beta(A) in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMV-rAct-injected mice. At the cellular level, loss of parietal cells was observed, resulting in increased pH within the stomach. This phenomenon was more severe in male than female mice. Consistent with damage of the stomach and intestine, activin beta(A) often led to necrosis in the tip of the tail or foot, and loss of body weight was observed in pCMV-rAct-injected male but not female mice. Finally, in pCMV-rAct-injected mice, circulating activin beta(A) led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin beta(A) has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin beta(A) must be controlled within a narrow range because of latent lethal activity. In addition, our approach can be used effectively for functional analysis of secreted proteins.