Octreotide modulates the effects on fibrosis of TNF-α, TGF-β and PDGF in activated rat hepatic stellate cells
Copyright © 2013 Elsevier B.V. All rights reserved..
BACKGROUND AND AIMS: Somatostatin and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide on cytokine activated hepatic stellate cells (HSC).
METHODS: Primary HSCs were isolated from rats and were cultured on plastic for activation. Expression of somatostatin receptors (SSTR) was investigated in cultured HSCs by immunofluorescence and western blot. The effect of octreotide on cellular proliferation was studied with the MTT assay and western blot for α1-procollagen (α1-PROC) production in TNFα, TGF-β1 or PDGF treated HSCs. Phosphotyrosine (PTP) and phosphoserine-phosphothreonine (STP) phosphatases inhibition was performed with sodium orthovanadate and okadaic acid respectively.
RESULTS: Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their expression is enhanced by further HSC activation. Octreotide did not have an effect on HSC proliferation but inhibited plastic induced α1-PROC production. Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and TGFβ1 dependent expression of α1-PROC, while an opposite effect was observed in TNFα-induced cell proliferation and collagen production. PTP inhibition reversed the inhibitory effect of octreotide on α1-PROC, but potentiated its effect on PDGF and TGFβ1 dependent α1-PROC production. Finally, STP inhibition profoundly inhibited α1-PROC expression in all cases suggesting that both STP and PTP phosphatases are important regulators of pro-fibrotic mechanisms.
CONCLUSIONS: The net effect of octreotide on HSCs and therefore liver fibrosis is subject to the cytokine microenvironment of these cells. This effect is modulated by PTPs and STPs inhibition. Especially in the case of STPs their profibrotic effects could be an interesting new therapeutic target in liver fibrosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:188 |
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| Enthalten in: |
Regulatory peptides - 188(2014) vom: 10. Jan., Seite 5-12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Klironomos, Stefanos [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.10.2014 Date Revised 24.02.2014 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.regpep.2013.11.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM233212795 |
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| 100 | 1 | |a Klironomos, Stefanos |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Octreotide modulates the effects on fibrosis of TNF-α, TGF-β and PDGF in activated rat hepatic stellate cells |
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| 500 | |a Date Completed 21.10.2014 | ||
| 500 | |a Date Revised 24.02.2014 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2013 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND AND AIMS: Somatostatin and its analogs may influence hepatic fibrosis interfering through several mechanisms. The aim of this study was to investigate the effect of octreotide on cytokine activated hepatic stellate cells (HSC) | ||
| 520 | |a METHODS: Primary HSCs were isolated from rats and were cultured on plastic for activation. Expression of somatostatin receptors (SSTR) was investigated in cultured HSCs by immunofluorescence and western blot. The effect of octreotide on cellular proliferation was studied with the MTT assay and western blot for α1-procollagen (α1-PROC) production in TNFα, TGF-β1 or PDGF treated HSCs. Phosphotyrosine (PTP) and phosphoserine-phosphothreonine (STP) phosphatases inhibition was performed with sodium orthovanadate and okadaic acid respectively | ||
| 520 | |a RESULTS: Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their expression is enhanced by further HSC activation. Octreotide did not have an effect on HSC proliferation but inhibited plastic induced α1-PROC production. Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and TGFβ1 dependent expression of α1-PROC, while an opposite effect was observed in TNFα-induced cell proliferation and collagen production. PTP inhibition reversed the inhibitory effect of octreotide on α1-PROC, but potentiated its effect on PDGF and TGFβ1 dependent α1-PROC production. Finally, STP inhibition profoundly inhibited α1-PROC expression in all cases suggesting that both STP and PTP phosphatases are important regulators of pro-fibrotic mechanisms | ||
| 520 | |a CONCLUSIONS: The net effect of octreotide on HSCs and therefore liver fibrosis is subject to the cytokine microenvironment of these cells. This effect is modulated by PTPs and STPs inhibition. Especially in the case of STPs their profibrotic effects could be an interesting new therapeutic target in liver fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Fibrosis | |
| 650 | 4 | |a Hepatic stellate cells | |
| 650 | 4 | |a Procollagen | |
| 650 | 4 | |a Somatostatin | |
| 650 | 4 | |a Somatostatin receptors | |
| 650 | 7 | |a Phosphoproteins |2 NLM | |
| 650 | 7 | |a Platelet-Derived Growth Factor |2 NLM | |
| 650 | 7 | |a Receptors, Somatostatin |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Collagen |2 NLM | |
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| 650 | 7 | |a Protein Tyrosine Phosphatases |2 NLM | |
| 650 | 7 | |a EC 3.1.3.48 |2 NLM | |
| 650 | 7 | |a Octreotide |2 NLM | |
| 650 | 7 | |a RWM8CCW8GP |2 NLM | |
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| 700 | 1 | |a Sfakianaki, Ourania |e verfasserin |4 aut | |
| 700 | 1 | |a Kiagiadaki, Foteini |e verfasserin |4 aut | |
| 700 | 1 | |a Xidakis, Costas |e verfasserin |4 aut | |
| 700 | 1 | |a Kouroumalis, Elias |e verfasserin |4 aut | |
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