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The Hormonal Effect of Fibroblast Growth Factor 19 on the Intestinal Adaptation in Pediatric Short Bowel Syndrome: An
Yiming Gong1, Yang Wang2, Yuling Zhao1
1Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Insights
Fibroblast growth factor 19 (FGF19) enhances intestinal adaptation in short bowel syndrome (SBS) by improving epithelial barrier and mitochondrial function, and regulating cell adhesion.
Area of Science:
- Gastroenterology
- Pediatric Medicine
- Molecular Biology
Background:
- Intestinal adaptation is crucial for pediatric patients with short bowel syndrome (SBS).
- The role of fibroblast growth factor 19 (FGF19) in SBS intestinal adaptation is not well understood.
Purpose of the Study:
- To investigate the hormonal effect of FGF19 on intestinal adaptation in pediatric short bowel syndrome.
Main Methods:
- Transcriptomic analyses of in vivo pediatric SBS patient datasets (with and without intact ileocecal valve).
- In vitro studies using short bowel syndrome patient-derived enteroids (SBS-PDEs) treated with recombinant human FGF19 (rhFGF19).
Main Results:
- Identified differentially expressed genes (DEGs) related to metabolic pathways and cell adhesion in vivo.
- rhFGF19 treatment in SBS-PDEs improved epithelial barrier integrity and mitochondrial respiration.
- 56 overlapping DEGs between in vivo and in vitro studies were primarily associated with cell adhesion.
Conclusions:
- FGF19 influences intestinal adaptation beyond metabolism.
- FGF19 enhances epithelial barrier function and mitochondrial respiration in SBS.
- FGF19 plays a role in regulating cell adhesion for intestinal maturation.
Background:
Promoting intestinal adaptation is of paramount importance for restoring normal gastrointestinal function in pediatric patients with short bowel syndrome (SBS). However, the hormonal effect of fibroblast growth factor 19 (FGF19) on the intestinal adaptation of SBS patients remains unknown.
Methods:
Integrated analyses using transcriptomic profiles were performed across two datasets. In vivo datasets were obtained from a group of pediatric SBS patients without intact ileocecal valve (ICV) exhibiting immature gut function and reduced FGF19 levels (n = 5), compared to their counterparts with ICV (n = 4). In vitro datasets were obtained from SBS patients-derived enteroids (SBS-PDEs) treated with recombinant human FGF19 (rhFGF19).
Results:
As a result, 2680 differentially expressed genes (DEGs) were identified in vivo, most of which could be clustered into "metabolic pathway" and "cell adhesion"; 410 DEGs were identified in vitro, most of which could be clustered into "extracellular matrix organization" and "cell adhesion". In SBS-PDEs, treatment with rhFGF19 significantly enhanced the integrity of epithelial barrier function, and substantially improved the mitochondrial respiration function. Notably, there were 56 overlapped DEGs identified both in vitro and in vivo, most of which could be clustered into "cell adhesion".
Conclusions:
Beyond metabolic regulation, the hormonal effect of FGF19 on the maturation of intestinal epithelium may also include enhancing epithelial barrier function, improving mitochondrial respiration function, and regulating cell adhesion.
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