Apoptotic body engulfment by a human stellate cell line is profibrogenic

Ali Canbay, Pavel Taimr, Natalie Torok, Hajime Higuchi, Scott Friedman, Gregory James Gores

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-β (TGF-β), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in α-smooth muscle actin (primary cells), TGF-β1, and collagen α1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-β1 and collagen α1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen α1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.

Original languageEnglish (US)
Pages (from-to)655-663
Number of pages9
JournalLaboratory Investigation
Volume83
Issue number5
StatePublished - May 1 2003

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Cell Line
Hepatocytes
Transforming Growth Factors
Collagen
Messenger RNA
Extracellular Vesicles
Nocodazole
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Phosphatidylinositol 3-Kinases
Confocal Microscopy
Microtubules
Smooth Muscle
Liver Diseases
Actins
Rodentia
Chronic Disease
Phosphotransferases
Up-Regulation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Canbay, A., Taimr, P., Torok, N., Higuchi, H., Friedman, S., & Gores, G. J. (2003). Apoptotic body engulfment by a human stellate cell line is profibrogenic. Laboratory Investigation, 83(5), 655-663.

Apoptotic body engulfment by a human stellate cell line is profibrogenic. / Canbay, Ali; Taimr, Pavel; Torok, Natalie; Higuchi, Hajime; Friedman, Scott; Gores, Gregory James.

In: Laboratory Investigation, Vol. 83, No. 5, 01.05.2003, p. 655-663.

Research output: Contribution to journalArticle

Canbay, A, Taimr, P, Torok, N, Higuchi, H, Friedman, S & Gores, GJ 2003, 'Apoptotic body engulfment by a human stellate cell line is profibrogenic', Laboratory Investigation, vol. 83, no. 5, pp. 655-663.
Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Laboratory Investigation. 2003 May 1;83(5):655-663.
Canbay, Ali ; Taimr, Pavel ; Torok, Natalie ; Higuchi, Hajime ; Friedman, Scott ; Gores, Gregory James. / Apoptotic body engulfment by a human stellate cell line is profibrogenic. In: Laboratory Investigation. 2003 ; Vol. 83, No. 5. pp. 655-663.
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