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  Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity

Pivovarova-Ramich, O., Loske, J., Hornemann, S., Markova, M., Seebeck, N., Rosenthal, A., et al. (2021). Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity. Cells, 10: 1048. doi:10.3390/cells10051048.

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Pivovarova-Ramich_2021.pdf (Publisher version), 2MB
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Pivovarova-Ramich, Olga, Author
Loske, Jennifer , Author
Hornemann, Silke, Author
Markova, Mariya , Author
Seebeck, Nicole, Author
Rosenthal, Anke , Author
Klauschen, Frederick , Author
Castro, José Pedro, Author
Buschow, Rene1, Author              
Grune, Tilman , Author
Lange, Volker, Author
Rudovich, Natalia , Author
Ouwens, D. Margriet , Author
Affiliations:
1Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              

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Free keywords: WISP-1/CCN4; CCN proteins; adipokine; obesity; liver; fibrosis; inflammation; hepatic stellate cells
 Abstract: Liver fibrosis is a critical complication of obesity-induced fatty liver disease. Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4), a novel adipokine associated with visceral obesity and insulin resistance, also contributes to lung and kidney fibrosis. The aim of the present study was to investigate the role of CCN4 in liver fibrosis in severe obesity. For this, human liver biopsies were collected from 35 severely obese humans (BMI 42.5 ± 0.7 kg/m2, age 46.7 ± 1.8 y, 25.7% males) during bariatric surgery and examined for the expression of CCN4, fibrosis, and inflammation markers. Hepatic stellate LX-2 cells were treated with human recombinant CCN4 alone or in combination with LPS or transforming growth factor beta (TGF-β) and examined for fibrosis and inflammation markers. CCN4 mRNA expression in the liver positively correlated with BMI and expression of fibrosis markers COL1A1, COL3A1, COL6A1, αSMA, TGFB1, extracellular matrix turnover enzymes TIMP1 and MMP9, and the inflammatory marker ITGAX/CD11c. In LX-2 cells, the exposure to recombinant CCN4 caused dose-dependent induction of MMP9 and MCP1. CCN4 potentiated the TGF-β-mediated induction of COL3A1, TIMP1, and MCP1 but showed no interaction with LPS treatment. Our results suggest a potential contribution of CCN4 to the early pathogenesis of obesity-associated liver fibrosis.

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Language(s): eng - English
 Dates: 2021-04-272021-04-29
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3390/cells10051048
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Title: Cells
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI
Pages: - Volume / Issue: 10 Sequence Number: 1048 Start / End Page: - Identifier: CoNE: https://pure.mpg.de/cone/journals/resource/2073-4409