Abstract

Background/Aims Transforming growth factor-β (TGF-β) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-β play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-β on the contractility of activated HSCs. Methods Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-β1 in serum-free medium at 37 °C for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-α actin (SMA) content quantified and PKC activation studies conducted. Results TGF-β1 induced a time- and dose-dependent decrease in lattice area up to 40% of control (P<0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in these cells. Furthermore, pre-incubating with a PKC-ε-specific inhibitor completely abrogated the TGF-β-induced contraction. Conclusions TGF-β induces contraction of activated HSCs via an increase in SMA content and a PKC-ε-mediated pathway.

Original languageEnglish (US)
Pages (from-to)60-66
Number of pages7
JournalJournal of Hepatology
Volume41
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

Hepatic Stellate Cells
Transforming Growth Factors
Smooth Muscle
Actins
Gels
Serum-Free Culture Media
Portal Hypertension
Collagen
Cytokines
Cell Line
Liver
Wounds and Injuries

Keywords

  • Alcoholic liver injury
  • Collagen lattice
  • Hepatic stellate cells
  • PKC-ε
  • Portal hypertension
  • Protein kinase C
  • Smooth muscle α actin
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Hepatology

Cite this

Transforming growth factor-β induces contraction of activated hepatic stellate cells. / Kharbanda, Kusum; Rogers, David D.; Wyatt, Todd A; Sorrell, Michael Floyd; Tuma, Dean J.

In: Journal of Hepatology, Vol. 41, No. 1, 01.07.2004, p. 60-66.

Research output: Contribution to journalArticle

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abstract = "Background/Aims Transforming growth factor-β (TGF-β) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-β play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-β on the contractility of activated HSCs. Methods Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-β1 in serum-free medium at 37 °C for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-α actin (SMA) content quantified and PKC activation studies conducted. Results TGF-β1 induced a time- and dose-dependent decrease in lattice area up to 40{\%} of control (P<0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in these cells. Furthermore, pre-incubating with a PKC-ε-specific inhibitor completely abrogated the TGF-β-induced contraction. Conclusions TGF-β induces contraction of activated HSCs via an increase in SMA content and a PKC-ε-mediated pathway.",
keywords = "Alcoholic liver injury, Collagen lattice, Hepatic stellate cells, PKC-ε, Portal hypertension, Protein kinase C, Smooth muscle α actin, Transforming growth factor-β",
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T1 - Transforming growth factor-β induces contraction of activated hepatic stellate cells

AU - Kharbanda, Kusum

AU - Rogers, David D.

AU - Wyatt, Todd A

AU - Sorrell, Michael Floyd

AU - Tuma, Dean J.

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N2 - Background/Aims Transforming growth factor-β (TGF-β) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-β play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-β on the contractility of activated HSCs. Methods Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-β1 in serum-free medium at 37 °C for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-α actin (SMA) content quantified and PKC activation studies conducted. Results TGF-β1 induced a time- and dose-dependent decrease in lattice area up to 40% of control (P<0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in these cells. Furthermore, pre-incubating with a PKC-ε-specific inhibitor completely abrogated the TGF-β-induced contraction. Conclusions TGF-β induces contraction of activated HSCs via an increase in SMA content and a PKC-ε-mediated pathway.

AB - Background/Aims Transforming growth factor-β (TGF-β) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-β play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-β on the contractility of activated HSCs. Methods Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-β1 in serum-free medium at 37 °C for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-α actin (SMA) content quantified and PKC activation studies conducted. Results TGF-β1 induced a time- and dose-dependent decrease in lattice area up to 40% of control (P<0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P<0.05) and PKC activation (5-fold, P<0.05) in these cells. Furthermore, pre-incubating with a PKC-ε-specific inhibitor completely abrogated the TGF-β-induced contraction. Conclusions TGF-β induces contraction of activated HSCs via an increase in SMA content and a PKC-ε-mediated pathway.

KW - Alcoholic liver injury

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