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Cystatin C prevents tissue injury after lung transplantation.
Life Sci. All. 9:e202503312 (2026)
Lung transplantation (LTx) offers life-saving therapy for end-stage lung disease, yet primary graft dysfunction (PGD) and bronchiolitis obliterans syndrome remain major complications, which limit long-term outcomes. The risk of PGD increases with prolonged storage and reperfusion injury. This study investigated the protective effects of cystatin C (CysC), a cysteine protease inhibitor, against PGD, through neutralization of cathepsin B activity. LTx recipients exhibited reduced levels of CysC and greater lung damage reflected by increased γ-H2AX and ACSL4 expression, correlating with poorer outcome. Using an orthotopic LTx model, we engineered CysC-Alb, an albumin-fused, cell-permeable CysC derivative for enhanced lung preservation. Adding CysC-Alb to preservation solutions during cold storage and ex vivo lung perfusion improved oxygenation, reduced DNA damage, and minimized cell death, particularly in alveolar type 2 cells. In murine grafts, CysC-Alb decreased γ-H2AX and ACSL4 expression, markers of DNA damage and ferroptosis, respectively. These findings highlight CysC-Alb as an effective additive to mitigate early pulmonary dysfunction after LTx and improve lung graft viability and transplantation outcomes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Half-life; Donor; Preservation
ISSN (print) / ISBN
2575-1077
e-ISSN
2575-1077
Journal
Life Science Alliance
Quellenangaben
Volume: 9,
Issue: 2,
Article Number: e202503312
Publisher
EMBO Press
Publishing Place
Heidelberg
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
Grants
Deutsches Zentrum fr Lungenforschung (DZL)