PUBLICATION
R-Spondin1 enhances wnt signaling and decreases weight loss in short bowel syndrome zebrafish
- Authors
- Maselli, K.M., Levin, G., Gee, K.M., Leeflang, E.J., Carreira, A.C.O., Sogayar, M.C., Grikscheit, T.C.
- ID
- ZDB-PUB-210114-14
- Date
- 2021
- Source
- Biochemistry and biophysics reports 25: 100874 (Journal)
- Registered Authors
- Keywords
- Cyclin D1, Intestinal adaptation, R-spondin1, Short bowel syndrome, Wnt, Zebrafish
- MeSH Terms
- none
- PubMed
- 33437880 Full text @ Biochem Biophys Rep
Citation
Maselli, K.M., Levin, G., Gee, K.M., Leeflang, E.J., Carreira, A.C.O., Sogayar, M.C., Grikscheit, T.C. (2021) R-Spondin1 enhances wnt signaling and decreases weight loss in short bowel syndrome zebrafish. Biochemistry and biophysics reports. 25:100874.
Abstract
Background R-spondins, including R-spondin 1 (RSPO1), are a family of Wnt ligands that help to activate the canonical Wnt/β-catenin pathway, which is critical for intestinal epithelial cell proliferation and maintenance of intestinal stem cells. This proliferation underpins the epithelial expansion, or intestinal adaptation (IA), that occurs following massive bowel resection and short bowel syndrome (SBS). The purpose of this study was to identify if recombinant human RSPO1 (rhRSPO1) could be serially administered to SBS zebrafish to enhance cellular proliferation and IA.
Methods Adult male zebrafish were assigned to four groups: sham + PBS, SBS + PBS, sham + rhRSPO1, and SBS + rhRSPO1. Sham fish had a laparotomy alone. SBS fish had a laparotomy with distal intestinal ligation and creation of a proximal stoma. Fish were weighed at initial surgery and then weekly. rhRSPO1 was administered post-operatively following either a one- or two-week dosing schedule with either 3 or 5 intraperitoneal injections, respectively. Fish were harvested at 7 or 14 days with intestinal segments collected for analysis.
Results Repeated intraperitoneal injection of rhRSPO1 was feasible and well tolerated. At 7 days, intestinal epithelial proliferation was increased by rhRSPO1. At 14 days, SBS + rhRSPO1 fish lost significantly less weight than SBS + PBS fish. Measurements of intestinal surface area were not increased by rhRSPO1 administration but immunofluorescent staining for β-catenin and gene expression for cyclin D1 was increased.
Conclusions Intraperitoneal injection of rhRSPO1 decreased weight loss in SBS zebrafish with increased β-catenin + cells and cyclin D1 expression at 14 days, indicating improved weight maintenance might result from increased activation of the canonical Wnt pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping