| [PMID]: | 27771159 |
| [Au] Autor: | Schall KA; Holoyda KA; Isani M; Lien CL; Al Alam D; Grikscheit TC |
| [Ad] Endereço: | Division of Pediatric Surgery and Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles and USC Keck School of Medicine, Los Angeles, CA. |
| [Ti] Título: | Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation. |
| [So] Source: | Surgery;161(3):694-703, 2017 03. |
| [Is] ISSN: | 1532-7361 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | 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. |
| [Mh] Termos MeSH primário: |
Proliferação Celular/fisiologia
Enterócitos/fisiologia
Fator 1 de Crescimento de Fibroblastos/fisiologia
Síndrome do Intestino Curto/patologia
Perda de Peso/fisiologia
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| [Mh] Termos MeSH secundário: |
Animais
Modelos Animais de Doenças
Intestino Delgado/metabolismo
Intestino Delgado/patologia
Masculino
Síndrome do Intestino Curto/etiologia
Síndrome do Intestino Curto/metabolismo
Transdução de Sinais/fisiologia
Peixe-Zebra
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 104781-85-3 (Fibroblast Growth Factor 1) |
| [Em] Mês de entrada: | 1707 |
| [Cu] Atualização por classe: | 180217 |
[Lr] Data última revisão:
| 180217 |
| [Sb] Subgrupo de revista: | AIM; IM |
| [Da] Data de entrada para processamento: | 161025 |
| [St] Status: | MEDLINE |
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