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- Title
Turnera diffusa extract attenuates profibrotic, extracellular matrix and mitochondrial markers in activated human hepatic stellate cells (HSC).
- Authors
Rodríguez-Rodríguez, Diana Raquel; Lozano-Sepulveda, Sonia Amelia; Delgado-Montemayor, Cecilia; Waksman, Noemí; Cordero-Perez, Paula; Rivas-Estilla, Ana María
- Abstract
Introduction and objectives: Hepatic fibrosis is characterized by the accumulation of extracellular matrix which includes the accumulation of α-smooth muscle actin (α-SMA), collagen type I (COL1α1), as well as remodeling induced by metalloproteinases and tissue inhibitor of metalloproteinase (TIMPs), where hepatic stellate cells (HSCs) play a central role. In addition, the transcription factor SNAI1 (which participates in epithelial-mesenchymal transition, EMT) and mitofusin 2 (MFN2, a mitochondrial marker) plays an important role in chronic liver disease. Turnera diffusa (TD), a Mexican endemic plant, has been shown to possess antioxidant and hepatoprotective activity in vitro. We treated human HSC (LX2 cells) with a methanolic extract of Turnera diffusa (METD) to evaluate the mechanism involved in its hepatoprotective effect measured as fibrosis modulation, EMT, and mitochondrial markers. Materials and methods: HSC LX-2 cells were treated with METD (100 and 200 ng/mL) alone or combined with TGF-α (10 ng/mL) at different time points (24, 48, and 72 h). α-SMA, COL1α1, MMP2, TIMP1, SNAI1, and MFN2 mRNAs and protein levels were determined by real-time quantitative PCR and Western Blot analysis. Results: We found that METD decreases COL1α1-mRNA, α-SMA, and TIMP1 protein expression in LX2 cells treated with and TGF-α. This treatment also decreases MFN2 and TIMP1 protein expression and induces overexpression of MMP2-mRNA. Conclusions: Our results suggest that a methanolic extract of Turnera diffusa is associated with an antifi- brotic effect by decreasing profibrotic and mitochondrial markers together with the possible induction of apoptosis through SNAI1 expression in activated HSC cells.
- Subjects
LIVER cells; EXTRACELLULAR matrix; MITOFUSIN 2; MITOCHONDRIA; WESTERN immunoblotting
- Publication
Annals of Hepatology: Official Journal of the Mexican Association of Hepatology, 2021, Vol 22, p1
- ISSN
1665-2681
- Publication type
Article
- DOI
10.1016/j.aohep.2020.10.009