The Adventures of Sonic Hedgehog in Development and Repair. I. Hedgehog signaling in gastrointestinal development and disease

Parkin, Caroline A.; Ingham, Philip W.

doi:10.1152/ajpgi.00457.2007

Cited by 48 publications

(29 citation statements)

References 27 publications

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“…Signalling is initiated by binding of one of the Hh proteins to the 12-pass transmembrane protein receptor Ptc, which is required to inhibit the activity of Smoothened (Smo), a seven-pass transmembrane protein, which is responsible for regulation of the zinc-finger-containing glioma-associated oncogene homologue (Gli) transcriptional effectors, Gli1, Gli2 and Gli3 [13,29]. Upon binding of Hh to Ptc, the Ptc-mediated inhibition of Smo is relieved [30,31]. This triggers a cascade that finally results in activation of the Gli family and transcription of Hh target genes, including Ptc and Gli itself [32].…”

Section: Discussionmentioning

confidence: 99%

“…Although it is not clear which regulatory effect explains this association, several hypotheses are possible. First, MADISON et al [34] demonstrated that ectopic expression of Hip in mice during fetal life was associated with expanded smooth muscle in the intestinal epithelium [31]. If the same effect were present in the small airways, then it could be speculated that changes in Hip influence the thickness of the airway muscle layer and induce more or less airflow limitation.…”

Section: Discussionmentioning

confidence: 99%

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Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study

Durme¹,

Eijgelsheim²,

Joos³

et al. 2009

European Respiratory Journal

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The Hedgehog signalling pathway plays an important role in lung morphogenesis and cellular responses to lung injury. A genome-wide association study has demonstrated that two single nucleotide polymorphisms (SNPs) near the Hedgehog-interacting protein (Hip) gene, SNP identifiers rs1828591 and rs13118928, are associated with risk of chronic obstructive pulmonary disease (COPD). The aim of the present study was to validate the observed association between genetic variation near the Hip gene and COPD, and to investigate whether risk estimates were modified by smoking behaviour.The association between the Hip gene SNPs and COPD was investigated in the Rotterdam Study by logistic regression analyses, adjusted for several covariates. In addition, an association meta-analysis was performed that included data from the genome-wide association study on COPD.Both SNPs were significantly associated with risk of COPD (OR 0.80; 95% CI 0.72-0.91). Homozygosity for the minor G allele resulted in a decreased risk of COPD of ,40% (95% CI 0.47-0.78). There was a significant interaction with the number of pack-years of smoking (p50.004). The meta-analysis yielded an odds ratio for COPD of 0.80 per additional G allele (p53.4610 -9 ).Genetic variation near the Hip gene was significantly associated with risk of COPD, depending on the number of pack-years of smoking.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study

Durme¹,

Eijgelsheim²,

Joos³

et al. 2009

European Respiratory Journal

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“…The hedgehog expression continues in the thicker pseudostratified epithelium of the ventromedial endoderm, which is adjacent to the lateral mesoderm (39). The fact that the inhibition of the hedgehog signals also leads to the ectopic appearance of the pancreatic structures in the organs such as the stomach and duodenum (45) indicates that this system also plays a role in determining the area in which the pancreas will develop. It has been shown that Notch signals stimulate exocrine cell differentiation, but suppress endocrine cell differentiation (46).…”

Section: Pancreas Developmentmentioning

confidence: 99%

Development of Liver and Pancreas

Eşrefoğlu¹,

Taşlıdere²,

Çetin³

2016

Bezmialem Science

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The parenchyma of the liver and pancreas is derived from the endoderm, whereas the stroma is derived from the mesoderm. Both of them are derived from the endoderm of the foregut as the esophagus, stomach, and a part of duodenum. At the 3 rd -4 th of development, the liver, gallbladder and bile ducts become diverticulum hepaticum that is derived from the caudal portion of the foregut. There were inductive effects of septum transversum and cardiac mesoderm for the development of liver diverticulum. The pancreas arise from the endoderm of the foregut. The pancreas is derived from the fusion of the ventral and dorsal pancreas bulbs, which arise from the endoderm of the duodenum. The inductive effects of the notochord and dorsal aorta play a role in the development of the pancreas. In this manuscript, we attempted to review the morphological and functional development of the liver and pancreas with the aid of pictures obtained from various stages of prenatal and postnatal development in the organs of rats.

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“…Hh ligands produced by gut epithelial cells act on receptors located on mesenchymal cells to activate downstream stromal target genes (41,42). Hhip, Gli-1, Gli-2, Gli-3, Patched 1 (Ptc-1), and Ptc-2 are stromal targets of Hh signals, and Hh signaling activity is best reflected by measuring Gli1, Ptc-1, and Hhip mRNA levels (42,43).…”

Section: Figurementioning

confidence: 99%

Epimorphin deletion protects mice from inflammation-induced colon carcinogenesis and alters stem cell niche myofibroblast secretion

Shaker¹,

Swietlicki²,

Wang³

et al. 2010

J. Clin. Invest.

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Epithelial-mesenchymal interactions regulate normal gut epithelial homeostasis and have a putative role in inflammatory bowel disease and colon cancer pathogenesis. Epimorphin is a mesenchymal and myofibroblast protein with antiproliferative, promorphogenic effects in intestinal epithelium. We previously showed that deletion of epimorphin partially protects mice from acute colitis, associated with an increase in crypt cell proliferation. Here we explored the potential therapeutic utility of modulating epimorphin expression by examining the effects of epimorphin deletion on chronic inflammation-associated colon carcinogenesis using the azoxymethane/dextran sodium sulfate (AOM/DSS) model. We found that mice in which epimorphin expression was absent had a marked reduction in incidence and extent of colonic dysplasia. Furthermore, epimorphin deletion in myofibroblasts altered the morphology and growth of cocultured epithelial cells. Loss of epimorphin affected secretion of soluble mesenchymal regulators of the stem cell niche such as Chordin. Importantly, IL-6 secretion from LPS-treated epimorphin-deficient myofibroblasts was completely inhibited, and stromal IL-6 expression was reduced in vivo. Taken together, these data show that epimorphin deletion inhibits chronic inflammation-associated colon carcinogenesis in mice, likely as a result of increased epithelial repair, decreased myofibroblast IL-6 secretion, and diminished IL-6-induced inflammation. Furthermore, we believe that modulation of epimorphin expression may have therapeutic benefits in appropriate clinical settings.

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The Adventures of Sonic Hedgehog in Development and Repair. I. Hedgehog signaling in gastrointestinal development and disease

Cited by 48 publications

References 27 publications

Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study

Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study

Development of Liver and Pancreas

Epimorphin deletion protects mice from inflammation-induced colon carcinogenesis and alters stem cell niche myofibroblast secretion

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