title: 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 βA on the body, including the gastro-intestinal (GI) tract. Initially, the activin βA protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin βA 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 βA 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 βA led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin βA has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin βA 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.
authors.affiliation: Department of Life Science, The Catholic University of Korea, Bucheon 14662, Korea.
authors.forename: Mi-Nyeu
authors.initials: MN
authors.lastname: Kim
authors.affiliation: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 130-872, Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: School of Life Science, Kwangju Institute of Science and Technology (K-JIST), Gwangju 500-712, Korea.
authors.forename: Chunghee
authors.initials: C
authors.lastname: Cho
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mayo
authors.affiliation: Department of Life Science, The Catholic University of Korea, Bucheon 14662, Korea.
authors.forename: Byung-Nam
authors.initials: BN
authors.lastname: Cho
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D028322:Inhibin-beta Subunits / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009336:Necrosis; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D012737:Sex Factors; D015431:Weight Loss
chemical_list: C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits
keywords: activin; digestion; endocrine; parietal cell; stomach