Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion
Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
MDPI
2022
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| _version_ | 1797106030436417536 |
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| author | van Leeuwen, L Venema, LH Heilig, R Leuvenink, HGD Kessler, BM |
| author_facet | van Leeuwen, L Venema, LH Heilig, R Leuvenink, HGD Kessler, BM |
| author_sort | van Leeuwen, L |
| collection | OXFORD |
| description | Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury. |
| first_indexed | 2024-03-07T06:55:53Z |
| format | Journal article |
| id | oxford-uuid:fe20e21b-faa1-4574-a460-f7e1fc52e2df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:55:53Z |
| publishDate | 2022 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:fe20e21b-faa1-4574-a460-f7e1fc52e2df2022-03-27T13:34:00ZDoxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fe20e21b-faa1-4574-a460-f7e1fc52e2dfEnglishSymplectic ElementsMDPI2022van Leeuwen, LVenema, LHHeilig, RLeuvenink, HGDKessler, BMIschemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury. |
| spellingShingle | van Leeuwen, L Venema, LH Heilig, R Leuvenink, HGD Kessler, BM Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title | Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title_full | Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title_fullStr | Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title_full_unstemmed | Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title_short | Doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| title_sort | doxycycline alters the porcine renal proteome and degradome during hypothermic machine perfusion |
| work_keys_str_mv | AT vanleeuwenl doxycyclinealterstheporcinerenalproteomeanddegradomeduringhypothermicmachineperfusion AT venemalh doxycyclinealterstheporcinerenalproteomeanddegradomeduringhypothermicmachineperfusion AT heiligr doxycyclinealterstheporcinerenalproteomeanddegradomeduringhypothermicmachineperfusion AT leuveninkhgd doxycyclinealterstheporcinerenalproteomeanddegradomeduringhypothermicmachineperfusion AT kesslerbm doxycyclinealterstheporcinerenalproteomeanddegradomeduringhypothermicmachineperfusion |