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Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
RGS16 Aggravates Hepatic Ischemia-Reperfusion Injury via Hepatocyte-Intrinsic Apoptosis/Inflammation & Neutrophil
Xinglong Li1,2,3, Zhanzhi Meng1,2, Hongjun Yu1,2
1Department of Minimally Invasive Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 28, 2026
Summary
Regulator of G-protein signaling 16 (RGS16) exacerbates liver injury after ischemia-reperfusion by boosting CXCL1 expression and neutrophil activity. Targeting RGS16 or its pathways may offer new therapies for hepatic ischemia-reperfusion injury (HIRI).
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- Hepatic ischemia-reperfusion injury (HIRI) is a severe complication following liver surgery and transplantation, characterized by sterile inflammation and limited treatment options.
- The role of Regulator of G-protein signaling 16 (RGS16), an inflammatory modulator, in HIRI has not been previously established.
Purpose of the Study:
- To investigate the role of RGS16 in the pathogenesis of HIRI.
- To elucidate the molecular mechanisms by which RGS16 influences liver injury and inflammation.
- To identify potential therapeutic targets for HIRI based on RGS16 signaling.
Main Methods:
- Analysis of RGS16 expression in post-hepatectomy patient livers and correlation with neutrophil extracellular trap formation (NETosis).
- Utilized hepatocyte-specific Rgs16 knockout and transgenic mouse models to assess liver injury following HIRI.
- Employed integrated multi-omics analyses (RNA-seq, MeRIP-seq, mass spectrometry) to identify RGS16 downstream effectors.
- Investigated the interaction of RGS16 with YTHDF3 and PAN3 to determine its effect on Cxcl1 mRNA stability.
- Assessed the impact of CXCL1 inhibition and NET degradation on RGS16-induced liver injury.
Main Results:
- RGS16 expression was elevated in HIRI patients and correlated with NETosis.
- RGS16 deficiency attenuated HIRI, while overexpression exacerbated liver injury.
- RGS16 was found to stabilize m6A-modified Cxcl1 mRNA by interacting with YTHDF3 and displacing PAN3, leading to increased CXCL1 expression.
- Elevated CXCL1 promoted hepatocyte apoptosis and inflammation via the CXCR2 pathway, driving neutrophil recruitment and NETosis.
- Pharmacological inhibition of CXCL1 or DNase I treatment significantly ameliorated RGS16-induced liver injury.
Conclusions:
- RGS16 aggravates HIRI by enhancing hepatocyte-intrinsic CXCL1-CXCR2 signaling.
- RGS16 amplifies CXCL1-mediated neutrophil recruitment and NETosis, contributing to liver damage.
- RGS16 and its downstream effectors represent promising therapeutic targets for managing HIRI.
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