ArticleAlcohol, clinical & experimental research2026
Calpain-4 Knockdown Modulates Cholesterol Metabolism and LXRα Nuclear Localization in Experimental Alcohol-Related Liver Disease.
Article in Alcohol, clinical & experimental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Update of
Authors and funding
12 authors.
Funding
Abstract
backgroundEthanol affects lipid metabolism through multiple pathways, leading to fatty liver development in most alcohol-related liver disease (ALD) patients. Recent studies have highlighted the role of calpain, a calcium-dependent protease, in liver inflammation and fibrosis. Calpain activity is regulated by its essential subunit, Capns1 (calpain-4), which stabilizes and modulates the activity of its catalytic isoforms, calpain-1 and calpain-2. This study investigated calpain's impact on lipid metabolism in ALD.
methodsSix-week-old C57Bl6/J mice were injected with rAAV8 vectors encoding Capns1 shRNA or control vectors. After 4 weeks, mice underwent a 10-day period of ad libitum ethanol consumption, followed by a single gavaged ethanol administration on day 11.
resultsCapns1 knockdown attenuated ethanol-induced microvesicular steatosis. Hepatic triglyceride and free fatty acid levels were not significantly altered, whereas cholesterol levels were significantly reduced in the ethanol group with Capns1 knockdown. Cpt1a expression increased significantly in the ethanol group with Capns1 knockdown. Western blot analysis revealed increased Cleaved-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) to Pro-HMGCR ratio in Capns1-knockdown mice, suggesting reduced HMGCR activity and suppressed cholesterol biosynthesis. LXRα expression was mainly increased in the cytoplasm in the ethanol group, and following Capns1 knockdown, it was relocalized to the nucleus via its activation. In addition, RNA sequencing analysis indicated that Capns1 knockdown contributes to the reprogramming of ethanol-induced disruptions in metabolic pathways, primarily those involving cholesterol metabolism.
conclusionFurther investigation into the relationship between Capns1 and cholesterol biosynthesis proteins may provide insights into using calpain inhibitors as a therapeutic approach for alcohol-related liver disease.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.