Cystatin C prevents tissue injury after lung transplantation

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.

Authors

Institutions

Publication Details

Journal
Life Science Alliance
Published
2025-11-28
DOI
https://doi.org/10.26508/lsa.202503312
Primary Topic
Transplantation: Methods and Outcomes
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Cystatin C prevents tissue injury after lung transplantation

Ali Doryab, Carmela Morrone, Natalia Smirnova, Thomas M. Conlon et al.
Life Science Alliance
Transplantation: Methods and Outcomes
article

Cystatin C prevents tissue injury after lung transplantation

Ali Doryab, Carmela Morrone, Natalia Smirnova, Thomas M. Conlon, Aicha Jeridi, Dieter E. Jenne, Carlo Mümmler, Nikolaus Kneidinger, Salome R. T. Rehm, Otmar Schmid, Michael Gerckens, Henu Kumar Verma, Ali Önder Yildirim, Matthias Hecker, Alexey Dashkevich
article en

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.

Life Science AllianceVol. 9(2)
Inserm (FR), Justus-Liebig-Universität Gießen (DE), Medical University of Graz (AT), Leipzig Heart Institute (DE), German Center for Lung Research (DE), Universities of Giessen and Marburg Lung Center (DE), Max Planck Institute for Intelligent Systems (DE), Centre of Experimental Medicine of the Slovak Academy of Sciences (SK), Institut des Maladies Métaboliques et Cardiovasculaires (FR), Cardio-Pulmonary Institute (DE), Urologische Klinik München (DE), Ludwig-Maximilians-Universität München (DE)
Deutsches Zentrum für Lungenforschung
Openalex Percentile: Top 40%
Transplantation: Methods and Outcomes
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.