Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice

Ochoa, Begoña; Syn, Wing–Kin; Delgado, Igotz; Karaca, Gamze; Jung, Youngmi; Wang, Jiangbo; Zubiaga, Ana M.; Fresnedo, Olatz; Omenetti, Alessia; Zdanowicz, Marzena; Choi, Steve S.; Diehl, Anna Mae

doi:10.1002/hep.23525

Cited by 159 publications

(173 citation statements)

References 44 publications

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“…Here also, HH signaling activation is one of the steps towards tissue reconstruction following injury (Omenetti et al, 2007). After partial hepatectomy, canonical HH signaling is required for hepatocyte proliferation; blocking of the HH pathway with the SMO inhibitor cyclopamine decreases post-operative survival rates in mice (Ochoa et al, 2010). Upregulation of the pathway has been observed in the livers of individuals with primary biliary cirrhosis , also implicating HH signaling in the response to liver damage in humans.…”

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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“…Regulation of tissue regeneration involves the ligand-dependent activation of multiple growth factor pathways (1)(2)(3)(4). Release from extracellular storage is one of the most frequent mechanisms modulating the activity of these ligands (5).…”

mentioning

confidence: 99%

“…In this study, we used liver after partial hepatectomy (PH) as a model of tissue regeneration. This model has been extensively characterized at the biological level, and the kinetics of cell proliferation, and activation of ligands and pathways involved in the process of liver regeneration post-hepatectomy are well known (1)(2)(3)(4)16). However, the molecular mechanisms regulating the interplay between these ligand-activated pathways and the downstream effectors remain elusive.…”

mentioning

confidence: 99%

Activation of the Transcription Factor GLI1 by WNT Signaling Underlies the Role of SULFATASE 2 as a Regulator of Tissue Regeneration

Nakamura

Fernández‐Barrena

Ortiz-Ruiz

et al. 2013

Journal of Biological Chemistry

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Background: Tissue regeneration is a complex process involving a network of ligand-activated pathways. Results:The sulfatase SULF2 modulates cell proliferation and organ growth through a WNT-dependent activation of the transcription factor GLI1. Conclusion: Together, these data define a novel cascade regulating tissue regeneration. Significance: The knowledge derived from this study will contribute to the understanding of the molecular mechanisms modulating regeneration and organogenesis.

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“…Is it simply a bystander effect of injury (marker of injury), an ineffectual attempt at liver repair, or both? Inhibition of the Hh pathway in a mouse model of chronic injury led to an attenuated progenitor response and reduced fibrosis, 4 whereas blockade during acute liver injury resulted in a blunted progenitor response, impaired liver regeneration, and reduced survival, 5 suggesting that progenitors play a pivotal role in liver repair. Indeed, authors in this study noted that high levels of EpCAM-expressing progenitors may lead to improved outcomes after AH.…”

Section: Hedgehog-responsive Progenitors: Predictors Of Liver Outcomes?mentioning

confidence: 99%