miR-27b-3p aggravates steatohepatitis progression by targeting the Nrf2/HO-1 pathway
- 1College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
Abstract
Objective: The current study aimed to investigate whether miR-27b-3p regulates oxidative stress and inflammatory responses through the Nrf2/HO-1 signaling pathway during the progression of fatty liver. Liver tissues from dairy cows suffering from fatty liver and high-fat diet (HFD)-induced fatty liver mice were gathered to assess lipid accumulation, oxidative stress, inflammation, and the expression of miR-27b-3p and components of the Nrf2/HO-1 pathway.
Methods: Liver tissues from dairy cows with fatty liver and HFD-induced fatty liver mice were collected to evaluate lipid accumulation, oxidative stress, inflammation, and the expression of miR-27b-3p and components of the Nrf2/HO-1 pathway. An in vitro steatosis model was established in AML-12 hepatocytes using palmitic acid (PA). Oxidative stress markers (reactive oxygen species [ROS], superoxide dismutase [SOD], and malondialdehyde [MDA]), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and proteins associated with apoptosis were assessed. Bioinformatic analysis and dual-luciferase reporter assays were used to determine the interaction between miR-27b-3p and Nrf2. Functional assays were performed using miR-27b-3p mimetics and antagonists to evaluate its regulatory effects on the Nrf2/HO-1 signaling pathway and downstream cellular responses.
Results: Fatty liver tissues from dairy cows and HFD-fed mice exhibited significant lipid deposition, enhanced oxidative stress, and elevated inflammatory responses, accompanied by upregulation of miR-27b-3p expression and reduced Nrf2/HO-1 signaling activity. Comparable alterations were observed in PA-treated AML-12 cells. Bioinformatic analysis and dual-luciferase experiments validated that miR-27b-3p directly binds to the 3′ untranslated region of Nrf2. Inhibition of miR-27b-3p restored Nrf2 and HO-1 expression, reduced ROS and MDA levels, enhanced SOD activity, suppressed NF-κB activation, decreased pro-inflammatory cytokine production, and alleviated apoptosis. Conversely, the overexpression of miR-27b-3p further inhibited Nrf2/HO-1 signaling and exacerbated oxidative stress, inflammation, and cellular damage.
Conclusion: miR-27b-3p accelerates the progression of fatty liver toward steatohepatitis by directly inhibiting Nrf2 and downregulating the Nrf2/HO-1 antioxidant pathway, which increase oxidative stress, inflammatory responses, and hepatocyte apoptosis. These findings identify miR-27b-3p as a key upstream regulator of redox imbalance in fatty liver and suggest that targeting miR-27b-3p could be a promising strategy for the prevention and treatment of bovine fatty liver disease.
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BibTeX
@article{wang2026mir27b3p,
title = {{miR-27b-3p aggravates steatohepatitis progression by targeting the Nrf2/HO-1 pathway}},
author = {Kui Wang and Hao Pan and Yan Tian and Kangfeng Jiang and Xiaobing Li},
journal = {Animal Bioscience},
year = {2026},
month = jul,
doi = {10.5713/ab.260476},
url = {https://doi.org/10.5713/ab.260476},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - miR-27b-3p aggravates steatohepatitis progression by targeting the Nrf2/HO-1 pathway
AU - Kui Wang
AU - Hao Pan
AU - Yan Tian
AU - Kangfeng Jiang
AU - Xiaobing Li
PY - 2026
DA - 2026/07/27
JO - Animal Bioscience
DO - 10.5713/ab.260476
UR - https://doi.org/10.5713/ab.260476
AB - Objective: The current study aimed to investigate whether miR-27b-3p regulates oxidative stress and inflammatory responses through the Nrf2/HO-1 signaling pathway during the progression of fatty liver. Liver tissues from dairy cows suffering from fatty liver and high-fat diet (HFD)-induced fatty liver mice were gathered to assess lipid accumulation, oxidative stress, inflammation, and the expression of miR-27b-3p and components of the Nrf2/HO-1 pathway. Methods: Liver tissues from dairy cows with fatty liver and HFD-induced fatty liver mice were collected to evaluate lipid accumulation, oxidative stress, inflammation, and the expression of miR-27b-3p and components of the Nrf2/HO-1 pathway. An in vitro steatosis model was established in AML-12 hepatocytes using palmitic acid (PA). Oxidative stress markers (reactive oxygen species [ROS], superoxide dismutase [SOD], and malondialdehyde [MDA]), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and proteins associated with apoptosis were assessed. Bioinformatic analysis and dual-luciferase reporter assays were used to determine the interaction between miR-27b-3p and Nrf2. Functional assays were performed using miR-27b-3p mimetics and antagonists to evaluate its regulatory effects on the Nrf2/HO-1 signaling pathway and downstream cellular responses. Results: Fatty liver tissues from dairy cows and HFD-fed mice exhibited significant lipid deposition, enhanced oxidative stress, and elevated inflammatory responses, accompanied by upregulation of miR-27b-3p expression and reduced Nrf2/HO-1 signaling activity. Comparable alterations were observed in PA-treated AML-12 cells. Bioinformatic analysis and dual-luciferase experiments validated that miR-27b-3p directly binds to the 3′ untranslated region of Nrf2. Inhibition of miR-27b-3p restored Nrf2 and HO-1 expression, reduced ROS and MDA levels, enhanced SOD activity, suppressed NF-κB activation, decreased pro-inflammatory cytokine production, and alleviated apoptosis. Conversely, the overexpression of miR-27b-3p further inhibited Nrf2/HO-1 signaling and exacerbated oxidative stress, inflammation, and cellular damage. Conclusion: miR-27b-3p accelerates the progression of fatty liver toward steatohepatitis by directly inhibiting Nrf2 and downregulating the Nrf2/HO-1 antioxidant pathway, which increase oxidative stress, inflammatory responses, and hepatocyte apoptosis. These findings identify miR-27b-3p as a key upstream regulator of redox imbalance in fatty liver and suggest that targeting miR-27b-3p could be a promising strategy for the prevention and treatment of bovine fatty liver disease.
SN - 2765-0189
SN - 2765-0235
ER -