Upregulation of activin signaling in experimental colitis

You Qing Zhang, Silvia Resta, Barbara Jung, Kim E. Barrett, Nora E Sarvetnick

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/-mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume297
Issue number4
DOIs
StatePublished - Oct 13 2009

Fingerprint

Activins
Colitis
Follistatin
Up-Regulation
Dextran Sulfate
Epithelial Cells
Activin Receptors
Inflammation Mediators
Bromodeoxyuridine
Intestinal Mucosa
Growth
Inflammatory Bowel Diseases
Gastrointestinal Tract
Mucous Membrane
Epithelium
Immunohistochemistry
Macrophages
Cell Proliferation
Apoptosis
Hemorrhage

Keywords

  • Follistatin
  • Inflammation
  • Proliferation

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology
  • Medicine(all)

Cite this

Upregulation of activin signaling in experimental colitis. / Zhang, You Qing; Resta, Silvia; Jung, Barbara; Barrett, Kim E.; Sarvetnick, Nora E.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 297, No. 4, 13.10.2009.

Research output: Contribution to journalArticle

Zhang, You Qing ; Resta, Silvia ; Jung, Barbara ; Barrett, Kim E. ; Sarvetnick, Nora E. / Upregulation of activin signaling in experimental colitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2009 ; Vol. 297, No. 4.
@article{0db11ab8406b4cfc9bdbf24afccd8b38,
title = "Upregulation of activin signaling in experimental colitis",
abstract = "Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/-mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases.",
keywords = "Follistatin, Inflammation, Proliferation",
author = "Zhang, {You Qing} and Silvia Resta and Barbara Jung and Barrett, {Kim E.} and Sarvetnick, {Nora E}",
year = "2009",
month = "10",
day = "13",
doi = "10.1152/ajpgi.90631.2008",
language = "English (US)",
volume = "297",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Upregulation of activin signaling in experimental colitis

AU - Zhang, You Qing

AU - Resta, Silvia

AU - Jung, Barbara

AU - Barrett, Kim E.

AU - Sarvetnick, Nora E

PY - 2009/10/13

Y1 - 2009/10/13

N2 - Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/-mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases.

AB - Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/-mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases.

KW - Follistatin

KW - Inflammation

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=70349743989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349743989&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.90631.2008

DO - 10.1152/ajpgi.90631.2008

M3 - Article

VL - 297

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 4

ER -