PUBLICATION
Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation
- Authors
- Schall, K.A., Holoyda, K.A., Isani, M., Lien, C.L., Al Alam, D., Grikscheit, T.C.
- ID
- ZDB-PUB-161025-12
- Date
- 2017
- Source
- Surgery 161(3): 694-703 (Journal)
- Registered Authors
- Lien, Ching-Ling (Ellen)
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Proliferation/physiology*
- Disease Models, Animal
- Enterocytes/physiology*
- Fibroblast Growth Factor 1/physiology*
- Intestine, Small/metabolism
- Intestine, Small/pathology
- Male
- Short Bowel Syndrome/etiology
- Short Bowel Syndrome/metabolism
- Short Bowel Syndrome/pathology*
- Signal Transduction/physiology
- Weight Loss/physiology*
- Zebrafish
- PubMed
- 27771159 Full text @ Surgery
Citation
Schall, K.A., Holoyda, K.A., Isani, M., Lien, C.L., Al Alam, D., Grikscheit, T.C. (2017) Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation. Surgery. 161(3):694-703.
Abstract
Background Signaling by fibroblast growth factor is critical for epithelial proliferation, differentiation, and the development of many organs, including the intestine. Fibroblast growth factor 10 and fibroblast growth factor 2c are upregulated after massive bowel resection during intestinal adaptation. This pathway is conserved highly. We hypothesized that inhibition of fibroblast growth factor signaling would impair intestinal adaptation in the zebrafish model of short bowel syndrome and allow insight into the negative regulation of this pathway.
Methods Short bowel syndrome equivalent to a high jejunostomy was generated in adult male hsp70:dnfgfr1-GFP zebrafish, wildtype fish exposed to tyrosine-kinase inhibitor, and wildtype fish in absence of tyrosine-kinase inhibitor. Heat shock in hsp70:dnfgfr1-GFP fish decreases fgf 1 expression. Parameters including weight, proliferation, and differentiation were evaluated after harvest in experimental and control groups.
Results Although short bowel syndrome zebrafish lost more weight relative to sham zebrafish in both groups, heat shock fish with short bowel syndrome lost more weight compared with non-heat shock fish with short bowel syndrome. In the non-heat shock controls, the villus epithelial perimeter increased in short bowel syndrome compared with sham fish, but this did not occur in heat shock fish. Non-heat shock fish with short bowel syndrome fish had significantly increased Bromodeoxyuridine(+) proliferative cells per hemivillus compared with non-heat shock-sham, while heat shock-short bowel syndrome had a more substantial increase in Bromodeoxyuridine(+) cells compared with HS-sham. Non-heat shock-short bowel syndrome demonstrated a significantly increased percentage of Alcian blue(+) goblet cells per hemivillus compared with non-heat shock-sham, while the heat shock-short bowel syndrome demonstrated decreased Alcian blue(+) cells compared with non-heat shock-short bowel syndrome. In contrast, SU5402 inhibited epithelial proliferation while increasing weight loss.
Conclusion Inhibition of fibroblast growth factor-1 signaling in short bowel syndrome decreases epithelial adaptation, increases Bromodeoxyuridine-labeled cells at 2 weeks, and exacerbates weight loss while decreasing epithelial goblet cells.
Errata / Notes
This article is corrected by ZDB-PUB-220906-95 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping