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Updated: Oct 19, 2025
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Published on: May 23, 2021
Molecular and functional characterization of MST2 in grass carp during bacterial infection
Yanan Li1, Xiaolong Qiu1, Zhijie Lu1
1Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, 510222, USA.
Abstract:
The regulation of host redox homeostasis is critically important in the immune response to pathogens. The "mammalian sterile 20-like" kinase 2 (MST2) has been shown to play a role in apoptosis, cell proliferation, and cancer; however, few studies have examined its ability to modulate redox homeostasis during innate immunity, especially in teleost fish. In this study, we cloned the MST2 gene of Ctenopharyngodon idella (CiMST2) and analyzed its tissue distribution. CiMST2 was present in most of the studied tissues, and it was most highly expressed in brain tissue. Expression patterns analysis revealed that MST2 mRNA and protein were significantly up-regulated under bacterial infection, suggesting that it is involved in the immune response. Bacterial stimulation significantly increased the level of antioxidases. To explore the interplay between CiMST2 and antioxidant regulation, we examined the effects of CiMST2 overexpression and conducted RNA interference assays in vitro. CiMST2 overexpression significantly increased the expression levels of nuclear factor E2-related factor 2 (Nrf2) and other antioxidases and vice versa, revealing that CiMST2 regulated host redox homeostasis via Nrf2-antioxidant responsive element (ARE) signaling. Overall, our findings provide a new perspective on the role of MST2 in innate immunity in teleosts as well as insights that will aid the prevention and control of disease in the grass carp farming industry.
Insights
Mammalian sterile 20-like kinase 2 (MST2) plays a key role in the immune response of teleost fish. This study reveals MST2 regulates host redox homeostasis through the Nrf2-antioxidant responsive element signaling pathway.
Area of Science:
- Immunology
- Molecular Biology
- Fish Biology
Background:
- Host redox homeostasis is crucial for immune responses against pathogens.
- Mammalian sterile 20-like kinase 2 (MST2) is implicated in apoptosis, proliferation, and cancer, but its role in innate immunity and redox homeostasis in teleosts is understudied.
- Understanding MST2's function in fish immunity can inform disease management strategies.
Purpose of the Study:
- To clone and characterize the MST2 gene in Ctenopharyngodon idella (CiMST2).
- To investigate the role of CiMST2 in the innate immune response and its regulation of redox homeostasis in teleost fish.
- To elucidate the signaling pathway involved in CiMST2-mediated redox regulation.
Main Methods:
- Cloning and tissue distribution analysis of CiMST2 in Ctenopharyngodon idella.
- Analysis of MST2 mRNA and protein expression under bacterial infection.
- In vitro experiments involving CiMST2 overexpression and RNA interference (RNAi) assays.
- Measurement of antioxidase levels and Nrf2 (nuclear factor E2-related factor 2) expression.
Main Results:
- CiMST2 was found in most tissues, with highest expression in the brain.
- Bacterial infection significantly upregulated both MST2 mRNA and protein levels, indicating its involvement in the immune response.
- CiMST2 overexpression increased the expression of Nrf2 and antioxidases, while RNAi assays showed the opposite effect.
- CiMST2 was confirmed to regulate host redox homeostasis via the Nrf2-antioxidant responsive element (ARE) signaling pathway.
Conclusions:
- CiMST2 is a key regulator of innate immunity and redox homeostasis in teleost fish.
- The Nrf2-ARE signaling pathway is the mechanism by which CiMST2 modulates antioxidant responses.
- These findings offer new insights into fish innate immunity and potential strategies for disease control in aquaculture.
