Oncostatin M mediates STAT3-dependent intestinal epithelial restitution via increased cell proliferation, decreased apoptosis and upregulation of SERPIN family members

Publication

Oncostatin M mediates STAT3-dependent intestinal epithelial restitution via increased cell proliferation, decreased apoptosis and upregulation of SERPIN family members

Journal Paper/Review - Apr 7, 2014

Beigel Florian, Friedrich Matthias, Probst Corina, Sotlar Karl, Göke Burkhard, Diegelmann Julia, Brand Stephan

Citation

Beigel F, Friedrich M, Probst C, Sotlar K, Göke B, Diegelmann J, Brand S. Oncostatin M mediates STAT3-dependent intestinal epithelial restitution via increased cell proliferation, decreased apoptosis and upregulation of SERPIN family members. PloS one 2014; 9:e93498.

Type

Journal Paper/Review (English)

Journal

PloS one 2014; 9

Publication Date

Apr 7, 2014

Issn Electronic

1932-6203

Pages

e93498

Brief description/objective

OBJECTIVE
Oncostatin M (OSM) is produced by activated T cells, monocytes, and dendritic cells and signals through two distinct receptor complexes consisting of gp130 and LIFR (I) or OSMR-β and gp130 (II), respectively. Aim of this study was to analyze the role of OSM in intestinal epithelial cells (IEC) and intestinal inflammation.

METHODS
OSM expression and OSM receptor distribution was analyzed by PCR and immunohistochemistry experiments, signal transduction by immunoblotting. Gene expression studies were performed by microarray analysis and RT-PCR. Apoptosis was measured by caspases-3/7 activity. IEC migration and proliferation was studied in wounding and water soluble tetrazolium assays.

RESULTS
The IEC lines Caco-2, DLD-1, SW480, HCT116 and HT-29 express mRNA for the OSM receptor subunits gp130 and OSMR-β, while only HCT116, HT-29 and DLD-1 cells express LIFR mRNA. OSM binding to its receptor complex activates STAT1, STAT3, ERK-1/2, SAPK/JNK-1/2, and Akt. Microarray analysis revealed 79 genes that were significantly up-regulated (adj.-p ≤ 0.05) by OSM in IEC. Most up-regulated genes belong to the functional categories "immunity and defense" (p = 2.1 × 10(-7)), "apoptosis" (p = 3.7 × 10(-4)) and "JAK/STAT cascade" (p = 3.4 × 10(-6)). Members of the SERPIN gene family were among the most strongly up-regulated genes. OSM significantly increased STAT3- and MEK1-dependent IEC cell proliferation (p<0.05) and wound healing (p = 3.9 × 10(-5)). OSM protein expression was increased in colonic biopsies of patients with active inflammatory bowel disease (IBD).

CONCLUSIONS
OSM promotes STAT3-dependent intestinal epithelial cell proliferation and wound healing in vitro. Considering the increased OSM expression in colonic biopsy specimens of patients with active IBD, OSM upregulation may modulate a barrier-protective host response in intestinal inflammation. Further in vivo studies are warranted to elucidate the exact role of OSM in intestinal inflammation and the potential of OSM as a drug target in IBD.