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Published on: October 21, 2017
Selenium deficiency caused hepatitis in chickens via the miR-138-5p/SelM/ROS/Ca2+ overload pathway induced by
Xinyue Sun1, Wenyue Zhang1, Xu Shi1
1College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. shiwenxu@neau.edu.cn.
Abstract:
Selenoprotein M (SelM), a key thioredoxin like enzyme in the endoplasmic reticulum (ER), is closely related to hepatocyte degeneration. However, the role of miR-138-5p/SelM and necroptosis in chicken SelM-deficient hepatitis and the specific biological mechanism of liver inflammation caused by SelM deficiency have not been elucidated. We established an in vivo chicken liver Se deficiency model by feeding a low-Se diet. The miR-138-5p knockdown and overexpression models and SelM knockdown models were established in LMH cells for an in vitro study. Transmission electron microscopy, H&E staining, Fluo4-AM/ER staining, and flow cytometry were used to detect the morphological changes in chicken liver tissue and the expression changes of necroptosis and inflammation in chicken liver cells. We observed that Se deficiency resulted in liver inflammation, up-regulation of miR-138-5p expression and down-regulation of SelM expression in chickens. Oxidative stress, Ca2+ overload, energy metabolism disorder and necroptosis occurred in chicken liver tissue. Importantly, ROS and the Ca2+ inhibitor could effectively alleviate the energy metabolism disorder, necroptosis and inflammatory cytokine secretion caused by miR-138-5p overexpression and SelM knockdown in LMH cells. In conclusion, selenium deficiency causes hepatitis by upregulating miR-138-5p targeting SelM. Our research findings enrich our knowledge about the biological functions of SelM and provide a theoretical basis for the lack of SelM leading to liver inflammation in chickens.
Insights
Selenium deficiency causes chicken hepatitis by increasing miR-138-5p, which targets Selenoprotein M (SelM). This leads to oxidative stress, necroptosis, and liver inflammation.
Area of Science:
- Biochemistry
- Cell Biology
- Animal Science
Background:
- Selenoprotein M (SelM) is an endoplasmic reticulum enzyme linked to liver damage.
- The mechanism of SelM deficiency-induced hepatitis and the role of miR-138-5p in chickens remain unclear.
Purpose of the Study:
- To investigate the role of miR-138-5p/SelM axis in chicken liver inflammation caused by selenium deficiency.
- To elucidate the biological mechanisms underlying SelM deficiency-induced hepatitis in chickens.
Main Methods:
- Established in vivo chicken liver selenium deficiency model and in vitro LMH cell models for miR-138-5p and SelM manipulation.
- Utilized transmission electron microscopy, H&E staining, Fluo4-AM/ER staining, and flow cytometry to assess cellular and tissue changes.
- Measured oxidative stress markers, calcium ion levels, energy metabolism, and necroptosis indicators.
Main Results:
- Selenium deficiency in chickens led to liver inflammation, increased miR-138-5p, and decreased SelM expression.
- Observed oxidative stress, Ca2+ overload, energy metabolism disorder, and necroptosis in chicken liver tissue.
- Overexpression of miR-138-5p or knockdown of SelM in LMH cells induced similar pathological changes, which were ameliorated by ROS scavengers and Ca2+ inhibitors.
Conclusions:
- Selenium deficiency induces hepatitis in chickens by upregulating miR-138-5p, which targets and downregulates SelM.
- This pathway triggers oxidative stress, Ca2+ overload, energy metabolism disruption, and necroptosis, ultimately causing liver inflammation.
- Findings provide insights into SelM's biological functions and the pathogenesis of SelM deficiency-related liver disease in poultry.
