Molecular mechanism of modified KAT2A-mediated histone succinylation in asthma through inhibition of ferroptosis
Year: 2025
Type: article
Abstract: OBJECTIVE: KAT2A, as a kind of epigenetic enzyme, has been found to be involved in ferroptosis in recent years, so this research is to explore the role and molecular role of KAT2A-mediated modification of histone succinylation by inhibiting ferroptosis and its involvement in asthma. METHOD: An asthma model was established, and the expression of KAT2A, GPX4 and SLC7A11 proteins was analyzed by Western blot and qPCR; Masson staining, TUNEL staining and HE staining were used to observe the pathological changes of lung tissues; The Clone Formation Assay and Cell Counting Kit 8 (CCK-8) were used to assess the cell viability and proliferation; and ELISA was performed for the detection of inflammatory factors; Immune cells were counted with kits. The expression of ferroptosis indicators was evaluated using qPCR and Western blot; ChIP-qPCR was performed to analyze H3K79succ and RNA pol II on the SLC7A11 promoter. RESULTS: In vitro assays verified that KAT2A regulates asthma through ferroptosis; in vivo assays verified KAT2A-mediated IL-13 succinylation modification and its effect on asthma; KAT2A controls ferroptosis via SLC7A11 and subsequently regulates asthma; Erastin significantly increased the levels of Fe2+, lipid ROS, SOD, Iron, and MDA, and decreased the expression of GPX4 and SLC7A11 and reduced inflammatory response. CONCLUSIONS: The authors verified that KAT2A can reduce the inflammatory response caused by asthma, and further clarified that KAT2A-mediated histone succinylation modification participates in the occurrence of asthma by inhibiting ferroptosis, which may become a potential target for asthma treatment.
Source: Clinics
Authors: Jian Han, Hui-li Du, Shan-shan Lu, Jun-Feng Li
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,700
Award: G2267656136
OpenAlex ID: W4414709472