The Role of CTGF in Liver Fibrosis Induced in 3D Human Liver Spheroids.
NAFLD
NASH
PNPLA3
angiotensin II
hepatitis
metabolic syndrome
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 01 2023
13 01 2023
Historique:
received:
16
12
2022
revised:
09
01
2023
accepted:
11
01
2023
entrez:
21
1
2023
pubmed:
22
1
2023
medline:
25
1
2023
Statut:
epublish
Résumé
Connective tissue growth factor (CTGF) is involved in the regulation of extracellular matrix (ECM) production. Elevated levels of CTGF can be found in plasma from patients with liver fibrosis and in experimental animal models of liver fibrosis, but the exact role of CTGF in, e.g., diet-induced human liver fibrosis is not entirely known. To address this question, we utilized a 3D human liver co-culture spheroid model composed of hepatocytes and non-parenchymal cells, in which fibrosis is induced by TGF-β1, CTGF or free fatty acids (FFA). Treatment of the spheroids with TGF-β1 or FFA increased COL1A1 deposition as well as the expression of TGF-β1 and CTGF. Recombinant CTGF, as well as angiotensin II, caused increased expression and/or production of CTGF, TGF-β1, COL1A1, LOX, and IL-6. In addition, silencing of CTGF reduced both TGF-β1- and FFA-induced COL1A1 deposition. Furthermore, we found that IL-6 induced CTGF, COL1A1 and TGF-β1 production, suggesting that IL-6 is a mediator in the pathway of CTGF-induced fibrosis. Taken together, our data indicate a specific role for CTGF and CTGF downstream signaling pathways for the development of liver inflammation and fibrosis in the human 3D liver spheroid model.
Identifiants
pubmed: 36672237
pii: cells12020302
doi: 10.3390/cells12020302
pmc: PMC9857203
pii:
doi:
Substances chimiques
Connective Tissue Growth Factor
139568-91-5
Interleukin-6
0
Transforming Growth Factor beta1
0
CCN2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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