Corrigendum
Open Access | 
10.1172/jci.insight.167011
Differential role of MLKL in alcohol-associated and non–alcohol-associated fatty liver diseases in mice and humans
Tatsunori Miyata, Xiaoqin Wu, Xiude Fan, Emily Huang, Carlos Sanz-Garcia, Christina K. Cajigas-Du Ross, Sanjoy Roychowdhury, Annette Bellar, Megan R. McMullen, Jaividhya Dasarathy, Daniela S. Allende, Joan Caballeria, Pau Sancho-Bru, Craig J. McClain, Mack Mitchell, Arthur J. McCullough, Svetlana Radaeva, Bruce Barton, Gyongyi Szabo, Srinivasan Dasarathy, and Laura E. Nagy
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Published December 8, 2022 - More info
JCI Insight. 2022;7(23):e167011. https://doi.org/10.1172/jci.insight.167011.
© 2022 Miyata et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Abstract
Hepatocellular death contributes to progression of alcohol–associated (ALD-associated) and non–alcohol-associated (NAFL/NASH) liver diseases. However, receptor-interaction protein kinase 3 (RIP3), an intermediate in necroptotic cell death, contributes to injury in murine models of ALD but not NAFL/NASH. We show here that a differential role for mixed-lineage kinase domain–like protein (MLKL), the downstream effector of RIP3, in murine models of ALD versus NAFL/NASH and that RIP1-RIP3-MLKL can be used as biomarkers to distinguish alcohol-associated hepatitis (AH) from NASH. Phospho-MLKL was higher in livers of patients with NASH compared with AH or healthy controls (HCs). MLKL expression, phosphorylation, oligomerization, and translocation to plasma membrane were induced in WT mice fed diets high in fat, fructose, and cholesterol but not in response to Gao-binge (acute on chronic) ethanol exposure. Mlkl–/– mice were not protected from ethanol-induced hepatocellular injury, which was associated with increased expression of chemokines and neutrophil recruitment. Circulating concentrations of RIP1 and RIP3, but not MLKL, distinguished patients with AH from HCs or patients with NASH. Taken together, these data indicate that MLKL is differentially activated in ALD/AH compared with NAFL/NASH in both murine models and patients. Furthermore, plasma RIP1 and RIP3 may be promising biomarkers for distinguishing AH and NASH.
Authors
Tatsunori Miyata, Xiaoqin Wu, Xiude Fan, Emily Huang, Carlos Sanz-Garcia, Christina K. Cajigas-Du Ross, Sanjoy Roychowdhury, Annette Bellar, Megan R. McMullen, Jaividhya Dasarathy, Daniela S. Allende, Joan Caballeria, Pau Sancho-Bru, Craig J. McClain, Mack Mitchell, Arthur J. McCullough, Svetlana Radaeva, Bruce Barton, Gyongyi Szabo, Srinivasan Dasarathy, Laura E. Nagy
Original citation: JCI Insight. 2021;6(4):e140180. https://doi.org/10.1172/jci.insight.140180
Citation for this corrigendum: JCI Insight. 2022;7(23):e167011. https://doi.org/10.1172/jci.insight.167011
Following the publication of this article, the authors became aware of similarities between the CYP2E1 blot in Figure 4A and the pEIF2A blot in Figure 4B. After reviewing the original data, the authors determined that the pEIF2A blot in Figure 4B was incorrect and that this error was caused by misidentification of pEIF2A after reprobing of the CYP2E1 membrane for pEIF2A, CHOP, and GRP78. The authors have provided a correct version of Figure 4B with data obtained from a repeated experiment. This correct version appears below.
The authors regret the error.
