HST-1/FGF-4 plays a critical role in crypt cell survival and facilitates epithelial cell restitution and proliferation

Sasaki, Hideo; Hirai, Kotaro; Yamamoto, Hiroyasu; Tanooka, Hiroshi; Sanada, Hiromi; Iwamoto, Teruaki; Takahashi, Takeshi; Terada, Masaaki; Ochiya, Takahiro

doi:10.1038/sj.onc.1207348

Cited by 22 publications

(9 citation statements)

References 33 publications

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“…The intestinal epithelium has a rapid turnover and hence is severely affected by therapies targeting highly proliferative cells, such as radiation. FGF4 prevents radiation‐induced apoptosis in mouse intestine and increases the survival of crypt intestinal cells (Sasaki et al, ). FGF2, expressed in the mesenchymal cells surrounding the intestinal crypts, enhances the survival of the stem cells contained in the crypts following radiation injury (Houchen et al, ).…”

Section: Fgf and Intestinal Stem Cellsmentioning

confidence: 99%

Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Danopoulos

Schlieve

Grikscheit

et al. 2017

Developmental Dynamics

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Fibroblast growth factors (FGFs) are a family of conserved peptides that play an important role in the development, homeostasis, and repair processes of many organ systems, including the gastrointestinal tract. All four FGF receptors and several FGF ligands are present in the intestine. They play important roles in controlling cell proliferation, differentiation, epithelial cell restitution, and stem cell maintenance. Several FGFs have also been proven to be protective against gastrointestinal diseases such as inflammatory bowel diseases or to aid in regeneration after intestinal loss associated with short bowel syndrome. Herein, we review the multifaceted actions of canonical FGFs in intestinal development, homeostasis, and repair in rodents and humans. Developmental Dynamics 246:344–352, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Fgf and Intestinal Stem Cellsmentioning

confidence: 99%

Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Danopoulos

Schlieve

Grikscheit

et al. 2017

Developmental Dynamics

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“…1 Early in normal healing, epithelial cells at the edge of the injury flatten out, extend a lamellipodium and migrate across the extracellular matrix of the mucosal defect. 2 This migratory process is called restitution, and independent of cell proliferation, which begins later in healing, is regulated by cytokines, 3 growth factors, 4-7 and modulated by integrin-dependent interactions between adhesion molecules and matrix components. 8,9 One of the growth factors present at the wound site, transforming growth factor- β (TGF β ) is initially derived from accumulating platelets, but later can be overexpressed by epithelial cells involved in repairing the injury.…”

mentioning

confidence: 99%

Smad3 knockout mice exhibit impaired intestinal mucosal healing

Owen

Yuan

Basson

2008

Laboratory Investigation

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Altered transforming growth factor-β (TGFβ) expression may contribute to inflammatory bowel disease and modulate epithelial cell restitution. Interference with TGFβ-mediated signaling inhibits excisional skin wound healing, but accelerates healing of incisional cutaneous wounds and wounds in some other tissues. Therefore, we sought to clarify the potential role of Smad3-dependent TGFβ signaling in intestinal mucosal healing in Smad3 null mice. Jejunal serosal application of filter disks saturated with 75% acetic acid yielded a circumscribed reproducible ischemic mucosal ulcer 1 day later. We compared ulcer area at 3 and 5 days to day 1 in Smad3 knockout mice and syngeneic wild-type mice, and evaluated mucosal immunoreactivity at the ulcer edge for TGFβ, phosphorylated (activated) focal adhesion kinase (pFAK), phosphorylated extracellular signal-related kinase (pERK), proliferating cell nuclear antigen and apoptosis by TUNEL. Ulcer healing in Smad3 null mice was 17% less at day 3 (n = 14, P = 0.022) and 15% less at day 5 (n = 14, P = 0.004) than in wild-type littermates. In wild-type mice, pFAK, pERK and TGFβ immunoreactivity were elevated in epithelium immediately adjacent to the ulcer compared with more distant mucosa. However, this pattern of immunoreactivity for pFAK, pERK and TGFβ was not observed in Smad3 null mice. Smad3 null mice exhibited increased epithelial proliferation and no differences in apoptotic cell death compared with wild types, suggesting that ulcer healing may reflect differences in restitutive cell migration. Thus, Smad3-dependent disruption of the TGFβ signaling pathway impairs the healing of murine intestinal mucosal ulcers and alters patterns of activated FAK and ERK immunoreactivity important for cell migration at the ulcer edge. These studies suggest a significant role for Smad3-dependent TGFβ signaling in intestinal mucosal healing.

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“…These factors have been shown to protect cells against various cytotoxic injuries through their upregulation of anti-apoptotic proteins [45]. In mice, these factors have recently been tested for their ability to protect against radiation injury.…”

Section: Growth Factor Stimulationmentioning

confidence: 99%

Radiation-Induced Lung Injury Following Therapy for Thoracic Malignancy

Morgan¹,

Kachnic²,

Summer³

2005

CRMR

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Radiation therapy is a widely used treatment for locally advanced non-small cell lung cancer, as well as for a variety of other thoracic malignancies. Radiation induced lung injury (RILI) refers to any lung-related change resulting from this treatment. From a clinical standpoint, RILI is separated into two distinct syndromes: an acute pneumonitis beginning 2-10 weeks following RT and a more indolent fibrotic process, presenting months after initial exposure. A variety of factors have been identified that are associated with an increased risk of developing clinically significant RILI. These include treatment-related factors (dose and schedule of radiation, volume of lung irradiated, concurrent use of chemotherapy) and patient-related factors (age, gender, smoking status, presence of pre-existing lung disease). New insights into the mechanisms of radiation induced lung injury have been uncovered, and these findings have led to the development of novel strategies for the prevention and treatment of this complication. In this review, we will discuss the clinical manifestations and risk factors of RILI, and focus on recent advances in its pathogenesis and treatment.

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HST-1/FGF-4 plays a critical role in crypt cell survival and facilitates epithelial cell restitution and proliferation

Cited by 22 publications

References 33 publications

Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Fibroblast Growth Factors in the Gastrointestinal Tract: Twists and Turns

Smad3 knockout mice exhibit impaired intestinal mucosal healing

Radiation-Induced Lung Injury Following Therapy for Thoracic Malignancy

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