Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/74489
Title: MicroRNA-223 Suppresses Human Hepatic Stellate Cell Activation Partly via Regulating the Actin Cytoskeleton and Alleviates Fibrosis in Organoid Models of Liver Injury
Authors: Chaiyaboot Ariyachet
Nattaya Chuaypen
Pornchai Kaewsapsak
Naphat Chantaravisoot
Depicha Jindatip
Saranyapin Potikanond
Pisit Tangkijvanich
Authors: Chaiyaboot Ariyachet
Nattaya Chuaypen
Pornchai Kaewsapsak
Naphat Chantaravisoot
Depicha Jindatip
Saranyapin Potikanond
Pisit Tangkijvanich
Keywords: Biochemistry, Genetics and Molecular Biology;Chemical Engineering;Chemistry;Computer Science
Issue Date: 1-Aug-2022
Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate target mRNA expression, and altered expression of miRNAs is associated with liver pathological conditions. Recent studies in animal models have shown neutrophil/myeloid-specific microRNA-223 (miR-223) as a key regulator in the development of various liver diseases including fibrosis, where hepatic stellate cells (HSCs) are the key player in pathogenesis. However, the precise roles of miR-223 in human HSCs and its therapeutic potential to control fibrosis remain largely unexplored. Using primary human HSCs, we demonstrated that miR-223 suppressed the fibrogenic program and cellular proliferation while promoting features of quiescent HSCs including lipid re-accumulation and retinol storage. Furthermore, induction of miR-223 in HSCs decreased cellular motility and contraction. Mechanistically, miR-223 negatively regulated expression of smooth muscle α-actin (α-SMA) and thus reduced cytoskeletal activity, which is known to promote amplification of fibrogenic signals. Restoration of α-SMA in miR-223-overexpressing HSCs alleviated the antifibrotic effects of miR-223. Finally, to explore the therapeutic potential of miR-233 in liver fibrosis, we generated co-cultured organoids of HSCs with Huh7 hepatoma cells and challenged them with acetaminophen (APAP) or palmitic acid (PA) to induce hepatotoxicity. We showed that ectopic expression of miR-223 in HSCs attenuated fibrogenesis in the two human organoid models of liver injury, suggesting its potential application in antifibrotic therapy.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85137124466&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/74489
ISSN: 14220067
16616596
Appears in Collections:CMUL: Journal Articles

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