Exploring the Mechanisms of Cyclosporine Therapy in Aplastic Anemia: A Data‐Independent Acquisition Proteomics Approach
Year: 2025
Type: article
Abstract: RATIONALE: Clinically, cyclosporine (CsA) plays a crucial role in the treatment of aplastic anemia (AA) and has demonstrated significant therapeutic efficacy. We applied DIA-based quantitative proteomics to analyze plasma protein profiles in AA patients, aiming to identify proteins and pathways modulated by CsA, thereby elucidating its therapeutic mechanisms. METHODS: Plasma samples from three AA patients pre- and post-CsA treatment underwent data-independent acquisition proteomics. DEPs were identified using fold-change thresholds. Gene Ontology, KEGG, and STRING analyses revealed functional pathways and hub proteins, which were validated by ELISA in 13 AA patients. Molecular docking assessed CsA-core protein binding affinities. RESULTS: Compared to healthy people, AA patients exhibited 303 differential proteins, enriched in pathways related to oxidative stress, cellular adhesion, and energy dysregulation. Post-CsA treatment, 107 DEPs were identified, linked to redox balance and structural remodeling. Forty-eight proteins overlapped, with GAPDH, SOD1, CFL1, and ACTG1 as core targets. ELISA confirmed expression differences, and molecular docking showed strong CsA binding affinities to these proteins. CONCLUSIONS: Significant protein expression differences between AA patients and healthy controls suggest immune-related pathways, including metabolism, oxidative stress, and cell structure, as key treatment targets. CsA may regulate these to intervene in AA progression.
DOI: 10.1002/rcm.10085
Authors: Mingxin Guo, Ting Dai, Lin Wan, Xiang Sun, Zhiqiang Hu, Yanchun Chen
Institution: Yangzhou University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410859680