Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Verma, HK; Morrone, C; Rehm, SR; Jeridi, A; Smirnova, NF; Doryab, A; Weiß, SA; Dashkevich, A; Schmid, O; Mümmler, C; Gerckens, M; Conlon, TM; Hecker, M; Kneidinger, N; Jenne, DE; Yildirim, AÖ.
Cystatin C prevents tissue injury after lung transplantation.
Life Sci Alliance. 2026; 9(2):
Doi: 10.26508/lsa.202503312
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Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Kneidinger Nikolaus
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Cystatin C - pharmacology, metabolism
- Mice - administration & dosage
- Lung Transplantation - adverse effects, methods
- Male - administration & dosage
- Primary Graft Dysfunction - prevention & control
- Mice, Inbred C57BL - administration & dosage
- Lung - pathology, metabolism, drug effects
- Reperfusion Injury - prevention & control
- Humans - administration & dosage
- DNA Damage - drug effects
- Cathepsin B - metabolism
- Histones - metabolism
- Bronchiolitis Obliterans - administration & dosage
- Organ Preservation - methods