Fate-Mapping Evidence That Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers

Yang, Liu; Jung, Youngmi; Omenetti, Alessia; Witek, Rafal P.; Choi, Steve S.; VanDongen, Hendrika M.A.; Huang, Jiawen; Alpini, Gianfranco; Diehl, Anna Mae

doi:10.1634/stemcells.2008-0115

Cited by 184 publications

(188 citation statements)

References 65 publications

Supporting

Mentioning

180

Contrasting

Order By: Relevance

“…The implication of this, at this time, is not entirely clear as a lineage relationship between LPCs and hepatic stellate cells has been proposed. 34 Regardless, we propose that a paracrine TWEAK-Fn14 signaling system operates in LPC-mediated liver regeneration, in which localized secretion of the TWEAK ligand by NK cells and macrophages regulates LPC behavior by binding and activating Fn14 on LPCs.…”

Section: Discussionmentioning

confidence: 97%

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Tirnitz–Parker¹,

Viebahn²,

Jakubowski³

et al. 2010

Hepatology

160

182

View full text Add to dashboard Cite

Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor–like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin–positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFκB subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFκB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (Hepatology 2010)

show abstract

Section: Discussionmentioning

confidence: 97%

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Tirnitz–Parker¹,

Viebahn²,

Jakubowski³

et al. 2010

Hepatology

160

182

View full text Add to dashboard Cite

show abstract

“…It remains that CK19-negative cells expressing mesenchymal markers were detected in close proximity to LPC, confirming that LPC are accompanied by aSMA-positive cells that derive from HSC or periportal fibroblasts. 10,11,15 Other evidence suggests that HSC could differentiate into LPC with an intermediate phenotype, 51,57 adding further complexity to the mechanisms by which HSC or LPC contribute to liver fibrogenesis. Nevertheless, mesenchymal-to-epithelial transition of HSC could not be demonstrated in liver fibrosis induced by bile duct ligation or CCl 4 administration.…”

Section: Discussionmentioning

confidence: 99%

Liver precursor cells increase hepatic fibrosis induced by chronic carbon tetrachloride intoxication in rats

Chobert

Couchie

Fourcot

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

“…8 A recent study provided additional hints that HSCs are directly involved in restoration of liver mass also in vivo. 9 Moreover, HSCs possess signaling pathways required for stem cell functions such as hedgehog and ␤-catenin-dependent Wnt signaling. 10,11 Similar to hematopoietic stem cells, quiescent HSCs are resistant against CD95-mediated apoptosis and proliferate in response to CD95 ligand.…”

Section: S Tellate Cells Reside Within the Perisinusoidal Space Ofmentioning

confidence: 99%

The niche of stellate cells within rat liver #

et al. 2009

View full text Add to dashboard Cite

Fate-Mapping Evidence That Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers

Abstract: Liver injury activates quiescent hepatic stellate cells (Q-HSC

Cited by 184 publications

References 65 publications

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Liver precursor cells increase hepatic fibrosis induced by chronic carbon tetrachloride intoxication in rats

The niche of stellate cells within rat liver #

Contact Info

Product

Resources

About