Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Danopoulos, Soula; Schlieve, Christopher R.; Grikscheit, Tracy C.; Alam, Denise Al

doi:10.1002/dvdy.24491

Cited by 46 publications

(37 citation statements)

References 95 publications

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“…These findings identified a novel Fgf2-IL-17 cross-talk that is important for intestinal injury repair (Song et al, 2015). This could be therapeutically relevant, given that Fgf1, -2, -7, -10 and -20 promote intestinal repair and reduce the inflammatory response in rodent models of colitis (reviewed by Danopoulos et al, 2017).…”

Section: Fgf Signaling In Intestinal Repairmentioning

confidence: 95%

“…A role for FGFs in intestinal repair has been suggested based on the strong overexpression of FGF7 in human inflammatory bowel disease, which is characterized by severe tissue damage in the intestine (reviewed by Danopoulos et al, 2017). The increased FGF7 levels most likely prevent more severe injury and promote intestinal epithelial repair, as mice lacking either Fgf7 or Fgf7producing intestinal γδ intraepithelial T lymphocytes are more susceptible to dextran sodium sulfate (DSS)-induced colitis than are wild-type controls, and they exhibit delayed repair of intestinal tissue after termination of the treatment .…”

Section: Fgf Signaling In Intestinal Repairmentioning

confidence: 99%

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Fibroblast growth factors: key players in regeneration and tissue repair

2017

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Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans.

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Section: Fgf Signaling In Intestinal Repairmentioning

confidence: 95%

Section: Fgf Signaling In Intestinal Repairmentioning

confidence: 99%

Fibroblast growth factors: key players in regeneration and tissue repair

2017

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“…During embryonic development and post-natally, multiple Fgf receptors and ligands are detected in the gastrointestinal tract. Fibroblast growth factor receptor 2b (Fgfr2b) ligands (encoded by Fgf1,3,7,10) are found in the embryonic as well as the adult mouse intestine [for review see Danopoulos et al (2017)]. During human development, up to 7 weeks of gestation, fibroblast growth factor 10 (FGF10) is detected mostly in the hindgut in the apical side of the epithelium while its expression is found to be decreased at later stages (Yin et al, 2013).…”

Section: Fgf Signaling Ligands and Receptorsmentioning

confidence: 99%

Role of FGF10/FGFR2b Signaling in Mouse Digestive Tract Development, Repair and Regeneration Following Injury

et al. 2019

Front. Cell Dev. Biol.

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During embryonic development, the rudimentary digestive tract is initially a tube-like structure. It is composed of epithelial cells surrounded by mesenchymal cells. Reciprocal epithelial-mesenchymal interactions progressively subdivide this primitive tube into distinct functional regions: the tongue, the pharynx, the esophagus, the stomach, the duodenum, the small intestine, the cecum, the large intestine, the colon, and the anus as well as the pancreas and the liver. Fibroblast growth factors (Fgfs) constitute a family of conserved small proteins playing crucial roles during organogenesis, homeostasis, and repair after injury. Among them, fibroblast growth factor 10 (Fgf10) has been reported to orchestrate epithelial-mesenchymal interactions during digestive tract development. In mice, loss of function of Fgf10 as well as its receptor fibroblast growth factor receptor 2b (Fgfr2b) lead to defective taste papillae in the tongue, underdeveloped and defective differentiation of the stomach, duodenal, cecal, and colonic atresias, anorectal malformation, as well as underdeveloped pancreas and liver. Fgf signaling through Fgfr2b receptor is also critical for the repair process after gut injury. In the adult mice, a malabsorption disorder called small bowel syndrome is triggered after massive small bowel resection (SBR). In wild-type mice, SBR leads to a regenerative process called gut adaptation characterized by an increase in the diameter of the remaining small intestine as well as by the presence of deeper crypts and longer villi, altogether leading to increased intestinal surface. Intestinal stem cells are key for this regeneration process. Induction of Fgf10 expression in the Paneth cells located in the crypt following SBR suggests a critical role for this growth factor in the process of gut adaptation.

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“…Therefore, FGF4 is a crucial growth factor, especially for the development of the placenta in mouse embryos, and Fgf4-null mice showed a peri-implantation lethal phenotype [3]. FGF4 also regulates organogenesis, including the development of the gastrointestinal tract, kidneys and teeth in fetuses [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Notably, FGF4 promoted the establishment of trophoblast stem cells from mouse blastocysts and the maintenance of trophoblast stem cells in an undifferentiated state in vitro [2]. FGF4 also promoted the generation of human intestinal organoids as threedimensional spheroids of human epithelium through directed differentiation of human embryonic stem cells and induced pluripotent stem cells [5,8,9]. Hence, FGF4 becomes more important not only in developmental biology but also in stem cell biology and regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

Site-directed mutagenesis of cysteine to serine residues affects heparin binding and mitogenicity in fibroblast growth factor 4 produced inEscherichia coli

Kumagai

Kikuchi

Nonaka

et al. 2019

Biotechnology & Biotechnological Equipment

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The binding activity to heparan sulphate is crucial for the mitogenic activity of fibroblast growth factor 4 (FGF4) in developing mammalian embryos. There are two conserved cysteine residues in FGF family proteins, Cys-84 and Cys-151 in mouse FGF4, and these constitute all of the cysteine residues in FGF4. However, the relationships among the heparin binding activity, growth promoting activity, and the two conserved cysteine residues in FGF4 are still unclear. Consequently, we generated in Escherichia coli three kinds of point-mutated mouse FGF4, namely C84S, C151S, and C84S;C151S, by converting the cysteine residues to serine residues. In heparin column chromatography, the heparin binding activities of these mutants were attenuated. In particular, the activity of the double-mutated C84S;C151S was weakened considerably. The growth promoting activities of these mutants correlated well with their heparin binding activities. We also demonstrated that an octapeptide, the Leu-76 to Tyr-83 region, which contained four basic amino acid residues and flanked Cys-84 in mouse FGF4, enhanced the heparin binding activity when fused to glutathione-S-transferase as a recombinant protein. Overall, our findings imply that the two conserved cysteine residues in FGF4 are both involved in the heparin binding activity and mitogenicity likely by affecting the configuration of heparin binding sites in FGF4.

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Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Cited by 46 publications

References 95 publications

Fibroblast growth factors: key players in regeneration and tissue repair

Fibroblast growth factors: key players in regeneration and tissue repair

Role of FGF10/FGFR2b Signaling in Mouse Digestive Tract Development, Repair and Regeneration Following Injury

Site-directed mutagenesis of cysteine to serine residues affects heparin binding and mitogenicity in fibroblast growth factor 4 produced inEscherichia coli

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