The role of hedgehog signaling during gastric regeneration

Kang, Dae-Hwan; Han, Myoung‐Eun; Song, Moo Ho; Lee, Young-Suk; Kim, Eun‐Hee; Kim, Hyun-Jung; Kim, Gwang-Ha; Kim, Dong-Heon; Yoon, Sik; Baek, Sun‐Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae‐Ock

doi:10.1007/s00535-009-0006-1

Cited by 37 publications

(36 citation statements)

References 30 publications

(32 reference statements)

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“…By contrast, upregulation of HH signaling by conditional removal of Ptch1 in adult colonic mesenchyme results in the depletion of the epithelial precursor cell pool due to premature differentiation (van Dop et al, 2009). Furthermore, HH signaling has been found to be downregulated during repair following gastric ulcer induction, whereas inhibition of SMO via cyclopamine treatment of injured mice further inhibits gastric progenitor cell differentiation (Kang et al, 2009). In mouse models of HH pathway inhibition, atrophy of the small intestinal villi is observed resulting from the loss of villus smooth muscle cells, which is also accompanied by inflammation and an increase in proliferation in the epithelial compartment (van Dop et al, 2010;Zacharias et al, 2010).…”

Section: Respiratory and Gastrointestinal Systemsmentioning

confidence: 99%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner.

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Section: Respiratory and Gastrointestinal Systemsmentioning

confidence: 99%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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“…9 Hh signaling is also critical for regeneration of several other organs such as stomach and exocrine pancreas. 11,12 In several of the tissues in which Hh is involved in renewal, pathway mis-activation has been linked to tumor formation. A similar role for Hh signaling in the development of salivary gland cancer has, so far, not been investigated.…”

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confidence: 99%

Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Fiaschi

Kolterud

Nilsson

et al. 2011

The American Journal of Pathology

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Hedgehog (Hh) signaling is a regulator of salivary gland morphogenesis, but its role in postnatal glands has only recently begun to be addressed. To examine the effects of deregulated Hh signaling in the salivary gland, we expressed the Hh effector protein GLI1, in salivary epithelial cells using both cytokeratin 5 and mouse mammary tumor virus (MMTV) transgenic systems. Ectopic pathway activation resulted in restrained acinar differentiation, formation of cystic lesions, and prominent appearance of ductal structures. Moreover, induced expression of GLI1 aids the formation of hyperplastic lesions, which closely resemble GLI1-induced changes in murine skin and mammary glands, suggesting that GLI1 targets cells with similar characteristics in different tissues. Furthermore, GLI1-expressing salivary epithelial cells are actively dividing, and GLI1-induced lesions are proliferative, an incident accompanied by enhanced expression of the Hh target genes, cyclin D1, and Snail. GLI1-induced salivary lesions regress after transgene withdrawal and become histologically normalized. Taken together, our data reveal the ability of GLI1 to modulate salivary acinar differentiation and to promote proliferation of ductal epithelial cells.

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“…Hh molecules (Sonic, Indian, and Desert Hedgehog) are important signaling proteins that play critical roles in the development and differentiation of many tissues and maintenance of adult SCs and CSCs [85,86]. Hh signaling is involved in the differentiation of gastric progenitor cells into mucous cells and parietal cells during the gastric ulcer repair process [85].…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

“…Cyclopamine, a specific inhibitor of Hh signaling, decreased the number of cells with the pit phenotype [96]. A recent study showed that cyclopamine significantly inhibited the differentiation of mucous cells and parietal cells during the gastric regeneration process; however, it did not affect their proliferation [85]. Further clues elucidating abnormal Shh signaling in the maintenance of GCSCs arose from a study by Song and coworkers, who isolated tumor sphere cells that showed an increased self-renewal capacity and chemoresistance, expressed CSC-related markers (CD44, CD24, and CD133), and had higher tumorigenic capacity in vivo.…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

“…Hh signaling is involved in the differentiation of gastric progenitor cells into mucous cells and parietal cells during the gastric ulcer repair process [85]. A loss of gastric tissue homeostasis resulting in Correa sequence is associated with the impairment of Sonic Hedgehog (Shh) within the acidsecreting glands in atrophic gastritis and intestinal metaplasia [87,88].…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

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Gastric cancer stem cells: therapeutic targets

et al. 2013

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During the past decade, a growing body of evidence has implied that cancer stem cells (CSCs) play an important role in the development of gastric cancer (GC). The notion that CSCs give rise to GC and may be responsible for invasion, metastasis, and resistance to treatment has profound implications for anti-cancer therapy. Recent major advances in the rapidly evolving field of CSCs have opened novel exciting opportunities for developing CSC-targeted therapies. Discovery of specific markers and signaling pathways in gastric CSCs (GCSCs), with the perfecting of technologies for identification, isolation, and validation of CSCs, may provide the basis for a revolutionary cancer treatment approach based on the eradication of GCSCs. Emerging therapeutic tools based on specific properties and functions of CSCs, including activation of self-renewal signaling pathways, differences in gene expression profiles, and increased activity of telomerase or chemoresistance mechanisms, are developing in parallel with advances in nanotechnology and bioengineering. The addition of GCSC-targeted therapies to current oncological protocols and their complementary application may be the key to successfully fighting GC.

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The role of hedgehog signaling during gastric regeneration

Abstract: The above results suggest that hedgehog signaling is involved in the differentiation of gastric progenitor cells during the gastric ulcer repair process.

Cited by 37 publications

References 30 publications

Roles for Hedgehog signaling in adult organ homeostasis and repair

Roles for Hedgehog signaling in adult organ homeostasis and repair

Targeted Expression of GLI1 in the Salivary Glands Results in an Altered Differentiation Program and Hyperplasia

Gastric cancer stem cells: therapeutic targets

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