Circ_0098181 binds PKM2 to attenuate liver fibrosis

Area of Science:

• Molecular Biology
• Hepatology
• RNA Biology

Background:

• Liver cirrhosis is a severe health concern, with fibrosis as its key pathological process.
• Circular RNAs (circRNAs) are implicated in liver fibrosis, but key players and mechanisms remain largely unknown.
• This study investigates the role and mechanism of circ_0098181 in liver fibrogenesis.

Purpose of the Study:

• To determine the effect of circ_0098181 on liver fibrogenesis.
• To elucidate the underlying molecular mechanisms of circ_0098181 in liver fibrosis.
• To explore circ_0098181 as a potential therapeutic target for liver cirrhosis.

Main Methods:

• RNA sequencing identified circRNA profiles in human cirrhotic tissues.
• In vitro (HSCs) and in vivo (CCl4-induced) models were used to assess circ_0098181 function.
• Mechanism elucidated via RNA pull-down, mass spectrometry, RIP, and qRT-PCR.

Main Results:

• Circ_0098181 levels were decreased in fibrotic liver tissues and activated hepatic stellate cells (HSCs).
• Exogenous circ_0098181 administration inhibited HSC activation, proliferation, migration, and ameliorated liver fibrosis.
• Circ_0098181 targets pyruvate kinase M2 (PKM2), inhibiting its nuclear translocation and phosphorylation, and suppresses pro-inflammatory cytokines.

Conclusions:

• Circ_0098181 exhibits significant anti-fibrotic effects in liver cirrhosis.
• The mechanism involves targeting PKM2 and inhibiting hepatic inflammation.
• Circ_0098181 holds promise as a therapeutic agent for liver cirrhosis.