PMID- 34829984 OWN - NLM STAT- MEDLINE DCOM- 20211216 LR - 20211216 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 22 DP - 2021 Nov 9 TI - Study of the Role of the Tyrosine Kinase Receptor MerTK in the Development of Kidney Ischemia-Reperfusion Injury in RCS Rats. LID - 10.3390/ijms222212103 [doi] LID - 12103 AB - Renal ischaemia reperfusion (I/R) triggers a cascade of events including oxidative stress, apoptotic body and microparticle (MP) formation as well as an acute inflammatory process that may contribute to organ failure. Macrophages are recruited to phagocytose cell debris and MPs. The tyrosine kinase receptor MerTK is a major player in the phagocytosis process. Experimental models of renal I/R events are of major importance for identifying I/R key players and for elaborating novel therapeutical approaches. A major aim of our study was to investigate possible involvement of MerTK in renal I/R. We performed our study on both natural mutant rats for MerTK (referred to as RCS) and on wild type rats referred to as WT. I/R was established by of bilateral clamping of the renal pedicles for 30' followed by three days of reperfusion. Plasma samples were analysed for creatinine, aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), kidney injury molecule -1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels and for MPs. Kidney tissue damage and CD68-positive cell requirement were analysed by histochemistry. monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and histone 3A (H3A) levels in kidney tissue lysates were analysed by western blotting. The phagocytic activity of blood-isolated monocytes collected from RCS or WT towards annexin-V positive bodies derived from cultured renal cell was assessed by fluorescence-activated single cell sorting (FACS) and confocal microscopy analyses. The renal I/R model for RCS rat described for the first time here paves the way for further investigations of MerTK-dependent events in renal tissue injury and repair mechanisms. FAU - Pele, Thomas AU - Pele T AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. FAU - Giraud, Sebastien AU - Giraud S AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Service de Biochimie, CHU Poitiers, 86000 Poitiers, France. FAU - Joffrion, Sandrine AU - Joffrion S AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Service de Biochimie, CHU Poitiers, 86000 Poitiers, France. FAU - Ameteau, Virginie AU - Ameteau V AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. FAU - Delwail, Adriana AU - Delwail A AD - Plateforme d'Imagerie de l'Universite de Poitiers et CNRS ERL 7003/EA 7349, Universite de Poitiers, 86000 Poitiers, France. FAU - Goujon, Jean-Michel AU - Goujon JM AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. AD - Service d'Anapathomopathologie, CHU Poitiers, 86000 Poitiers, France. FAU - Macchi, Laurent AU - Macchi L AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. AD - Service d'Hematologie, CHU Poitiers, 86000 Poitiers, France. FAU - Hauet, Thierry AU - Hauet T AUID- ORCID: 0000-0002-0117-071X AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Service de Biochimie, CHU Poitiers, 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. FAU - Dkhissi, Fatima AU - Dkhissi F AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. FAU - Benzakour, Omar AU - Benzakour O AD - INSERM U1082 (IRTOMIT), 86000 Poitiers, France. AD - Faculte de Medecine et de Pharmacie, Universite de Poitiers, 86000 Poitiers, France. LA - eng GR - 1082/Institut National de la Sante et de la Recherche Medicale/ PT - Journal Article DEP - 20211109 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Ccl2 protein, rat) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Havcr1protein, rat) RN - 0 (Lcn2 protein, rat) RN - 0 (Lipocalin-2) RN - 31C4KY9ESH (Nitric Oxide) RN - AYI8EX34EU (Creatinine) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.7.10.1 (Mertk protein, rat) RN - EC 2.7.10.1 (c-Mer Tyrosine Kinase) SB - IM MH - Acute Kidney Injury/blood/*genetics/pathology MH - Animals MH - Aspartate Aminotransferases/blood MH - Cell Adhesion Molecules/blood MH - Chemokine CCL2/blood MH - Creatinine/blood MH - Humans MH - Kidney/*metabolism/pathology MH - L-Lactate Dehydrogenase/blood MH - Lipocalin-2/blood MH - Macrophages/metabolism/pathology MH - Nitric Oxide/genetics MH - Nitric Oxide Synthase Type II/blood MH - Peroxidase/blood MH - Phagocytosis/genetics MH - Rats MH - Reperfusion Injury/blood/*genetics/pathology MH - c-Mer Tyrosine Kinase/*genetics PMC - PMC8618874 OTO - NOTNLM OT - MerTK OT - RCS rats OT - inflammation OT - ischemia-reperfusion OT - microparticles OT - phagocytosis COIS- The authors declare no conflict of interest. EDAT- 2021/11/28 06:00 MHDA- 2021/12/17 06:00 PMCR- 2021/11/09 CRDT- 2021/11/27 01:10 PHST- 2021/05/03 00:00 [received] PHST- 2021/05/31 00:00 [revised] PHST- 2021/11/03 00:00 [accepted] PHST- 2021/11/27 01:10 [entrez] PHST- 2021/11/28 06:00 [pubmed] PHST- 2021/12/17 06:00 [medline] PHST- 2021/11/09 00:00 [pmc-release] AID - ijms222212103 [pii] AID - ijms-22-12103 [pii] AID - 10.3390/ijms222212103 [doi] PST - epublish SO - Int J Mol Sci. 2021 Nov 9;22(22):12103. doi: 10.3390/ijms222212103.