[en] Renal ischemia/reperfusion (I/R) injury is a common clinical challenge faced by clinicians in kidney transplantation. I/R is the leading cause of acute kidney injury, and it occurs when blood flow to the kidney is interrupted and subsequently restored. I/R impairs renal function in both short and long terms. Renal ischemic preconditioning refers to all maneuvers intended to prevent or attenuate ischemic damage. In this context, the present review focuses on the dual-specificity phosphatase 3 (DUSP3), also known as vaccinia H1-related phosphatase, an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 has different biological functions: (1) it acts as a tumor modulator and (2) it is involved in the regulation of immune response, thrombosis, hemostasis, angiogenesis, and genomic stability. These functions occur either through MAPK-dependent or MAPK-independent mechanisms. DUSP3 genetic deletion dampens kidney damage and inflammation caused by I/R in mice, suggesting DUSP3 as a potential target for preventing renal I/R injury. Here, we discuss the putative role of DUSP3 in ischemic preconditioning and the potential mechanisms of such an attenuated inflammatory response via improved kidney perfusion and adequate innate immune response.
Disciplines :
Urology & nephrology
Author, co-author :
Khbouz, Badr; Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liège (ULiège), Liège, Belgium ; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Department of Medicine (Nephrology, Rheumatology, Endocrinology), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
MUSUMECI, Lucia ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie cardio-vasculaire et thoracique
Grahammer, Florian; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Department of Medicine (Nephrology, Rheumatology, Endocrinology), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Jouret, François ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Language :
English
Title :
The Dual-specificity Phosphatase 3 (DUSP3): A Potential Target Against Renal Ischemia/Reperfusion Injury.
Publication date :
08 April 2024
Journal title :
Transplantation
ISSN :
0041-1337
eISSN :
1534-6080
Publisher :
Ovid Technologies (Wolters Kluwer Health), United States
Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14:607–625.
Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121:4210–4221.
Shepherd HM, Gauthier JM, Terada Y, et al. Updated views on neutrophil responses in ischemia-reperfusion injury. Transplantation. 2022;106:2314–2324.
Erpicum P, Rowart P, Poma L, et al. Administration of mesenchymal stromal cells before renal ischemia/reperfusion attenuates kidney injury and may modulate renal lipid metabolism in rats. Sci Rep. 2017;7:8687.
Nieuwenhuijs-Moeke GJ, Pischke SE, Berger SP, et al. Ischemia and reperfusion injury in kidney transplantation: relevant mechanisms in injury and repair. J Clin Med. 2020;9:253.
Baaten CCFMJ, Meacham S, de Witt SM, et al. A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding. Blood. 2018;132:e35–e46.
Huang CY, Tan TH. DUSPs, to MAP kinases and beyond. Cell Biosci. 2012;2:24.
Monteiro LF, Ferruzo PYM, Russo LC, et al. DUSP3/VHR: a drug-gable dual phosphatase for human diseases. Rev Physiol Biochem Pharmacol. 2019;176:1–35.
Singh P, Dejager L, Amand M, et al. DUSP3 genetic deletion confers M2-like macrophage-dependent tolerance to septic shock. J Immunol. 2015;194:4951–4962.
Amand M, Erpicum C, Bajou K, et al. DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase. Mol Cancer. 2014;13:108.
Vandereyken MM, Singh P, Wathieu CP, et al. Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock. J Immunol. 2017;199:2515–2527.
Khbouz B, Rowart P, Poma L, et al. The genetic deletion of the dual specificity phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse. Acta Physiol (Oxf). 2022;234:e13735.
Tögel FE, Westenfelder C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol. 2010;6:179–183.
Kanagasundaram NS. Pathophysiology of ischaemic acute kidney injury. Ann Clin Biochem. 2015;52(Pt 2):193–205.
Legrand M, Rossignol P. Cardiovascular consequences of acute kidney injury. N Engl J Med. 2020;382:2238–2247.
Damman J, Bloks VW, Daha MR, et al. Hypoxia and complement- and-coagulation pathways in the deceased organ donor as the major target for intervention to improve renal allograft outcome. Transplantation. 2015;99:1293–1300.
Salahudeen AK, Haider N, May W. Cold ischemia and the reduced long-term survival of cadaveric renal allografts. Kidney Int. 2004;65:713–718.
Quiroga I, McShane P, Koo DD, et al. Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant. 2006;21:1689–1696.
Jayaram D, Kommareddi M, Sung RS, et al. Delayed graft function requiring more than one-time dialysis treatment is associated with inferior clinical outcomes. Clin Transplant. 2012;26:E536–E543.
Mikhalski D, Wissing KM, Ghisdal L, et al. Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression. Transplantation. 2008;85(7 Suppl):S3–S9.
Hosgood SA, Brown RJ, Nicholson ML. Advances in kidney preservation techniques and their application in clinical practice. Transplantation. 2021;105:e202–e214.
Burke M, Pabbidi MR, Farley J, et al. Molecular mechanisms of renal blood flow autoregulation. Curr Vasc Pharmacol. 2014;12:845–858.
Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17:1503–1520.
Erpicum P, Rowart P, Defraigne JO, et al. What we need to know about lipid-associated injury in case of renal ischemia-reperfusion. Am J Physiol Renal Physiol. 2018;315:F1714–F1719.
Jouret F, Leenders J, Poma L, et al. Nuclear magnetic resonance metabolomic profiling of mouse kidney, urine and serum following renal ischemia/reperfusion injury. PLoS One. 2016;11:e0163021.
Ogawa S, Koga S, Kuwabara K, et al. Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular cAMP levels. Am J Physiol. 1992;262(3 Pt 1):C546–C554.
Cassie S, Masterson MF, Polukoshko A, et al. Ischemia/reperfusion induces the recruitment of leukocytes from whole blood under flow conditions. Free Radic Biol Med. 2004;36:1102–1111.
Frangogiannis NG. Chemokines in ischemia and reperfusion. Thromb Haemost. 2007;97:738–747.
Rowart P, Erpicum P, Detry O, et al. Mesenchymal stromal cell therapy in ischemia/reperfusion injury. J Immunol Res. 2015;2015:602597.
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124–1136.
Cremers NA, Wever KE, Wong RJ, et al. Effects of remote ischemic preconditioning on heme oxygenase-1 expression and cutaneous wound repair. Int J Mol Sci. 2017;18:438.
Wever KE, Masereeuw R, Wagener FA, et al. Humoral signalling compounds in remote ischaemic preconditioning of the kidney, a role for the opioid receptor. Nephrol Dial Transplant. 2013;28:1721–1732.
Park KM, Chen A, Bonventre JV. Prevention of kidney ischemia/ reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem. 2001;276:11870–11876.
Khbouz B, Gu S, Pinto Coelho T, et al. Radiotherapy advances in renal disease-focus on renal ischemic preconditioning. Bioengineering (Basel). 2023;10:68.
Vandermeulen M, Erpicum P, Weekers L, et al. Mesenchymal stromal cells in solid organ transplantation. Transplantation. 2020;104:923–936.
Yang CW, Ahn HJ, Jung JY, et al. Preconditioning with cyclosporine A or FK506 differentially regulates mitogen-activated protein kinase expression in rat kidneys with ischemia/reperfusion injury. Transplantation. 2003;75:20–24.
Sugino H, Shimada H, Tsuchimoto K. Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats. Jpn J Pharmacol. 2001;87:134–142.
Hill P, Shukla D, Tran MG, et al. Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2008;19:39–46.
Bernhardt WM, Câmpean V, Kany S, et al. Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol. 2006;17:1970–1978.
Talab SS, Emami H, Elmi A, et al. Chronic lithium treatment protects the rat kidney against ischemia/reperfusion injury: the role of nitric oxide and cyclooxygenase pathways. Eur J Pharmacol. 2010;647:171–177.
Azarkish F, Nematbakhsh M, Fazilati M, et al. N-acetylcysteine prevents kidney and lung disturbances in renal ischemia/reperfusion injury in rat. Int J Prev Med. 2013;4:1139–1146.
Zahedi K, Barone S, Wang Y, et al. Proximal tubule epithelial cell specific ablation of the spermidine/spermine N1-acetyltransferase gene reduces the severity of renal ischemia/reperfusion injury. PLoS One. 2014;9:e110161.
Lieberthal W, Tang M, Lusco M, et al. Preconditioning mice with activators of AMPK ameliorates ischemic acute kidney injury in vivo. Am J Physiol Renal Physiol. 2016;311:F731–F739.
Huijink TM, Venema LH, Posma RA, et al. Metformin preconditioning and postconditioning to reduce ischemia reperfusion injury in an isolated ex vivo rat and porcine kidney normothermic machine perfusion model. Clin Transl Sci. 2021;14:222–230.
Chen HH, Lu PJ, Chen BR, et al. Heme oxygenase-1 ameliorates kidney ischemia-reperfusion injury in mice through extracellular signal-regulated kinase 1/2-enhanced tubular epithelium proliferation. Biochim Biophys Acta. 2015;1852(10 Pt A):2195–2201.
Khbouz B, Lallemand F, Cirillo A, et al. Kidney-targeted irradiation triggers renal ischemic preconditioning in mice. Am J Physiol Renal Physiol. 2022;323:F198–F211.
Franco-Acevedo A, Echavarria R, Moreno-Carranza B, et al. Opioid preconditioning modulates repair responses to prevent renal ischemia-reperfusion injury. Pharmaceuticals (Basel). 2020;13:387.
Abdel-Razek HA, Rizk MS, Amer GS, et al. Impact of combined ischemic preconditioning and melatonin on renal ischemia-reperfusion injury in rats. Iran J Basic Med Sci. 2023;26:235–240.
Hong YA, Jung SY, Yang KJ, et al. Cilastatin preconditioning attenuates renal ischemia-reperfusion injury via hypoxia inducible factor-1α activation. Int J Mol Sci. 2020;21:3583.
Bao N, Tang B, Wang J. Dexmedetomidine preconditioning protects rats from renal ischemia-reperfusion injury accompanied with biphasic changes of nuclear factor-kappa B signaling. J Immunol Res. 2020;2020:3230490.
Tian H, Tan R, Ye B, et al. SHP-1 inhibits renal ischemia reperfusion injury via dephosphorylating ASK1 and suppressing apoptosis. Biochem Biophys Res Commun. 2019;513:360–367.
Kierulf-Lassen C, Nieuwenhuijs-Moeke GJ, Krogstrup NV, et al. Molecular mechanisms of renal ischemic conditioning strategies. Eur Surg Res. 2015;55:151–183.
Yakulov TA, Todkar AP, Slanchev K, et al. CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury. Nat Commun. 2018;9:3660.
Erpicum P, Weekers L, Detry O, et al. Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study. Kidney Int. 2019;95:693–707.
Ishibashi T, Bottaro DP, Chan A, et al. Expression cloning of a human dual-specificity phosphatase. Proc Natl Acad Sci U S A. 1992;89:12170–12174.
Schumacher MA, Todd JL, Rice AE, et al. Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein phosphatase. Biochemistry. 2002;41:3009–3017.
Vandereyken M, Jacques S, Van Overmeire E, et al. Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner. PLoS One. 2017;12:e0185786.
Musumeci L, Kuijpers MJ, Gilio K, et al. Dual-specificity phosphatase 3 deficiency or inhibition limits platelet activation and arterial thrombosis. Circulation. 2015;131:656–668.
Jacques S, Arjomand A, Perée H, et al. Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma. Sci Rep. 2021;11:5817.
Jiang A, Zhao C, Zhang D, et al. Dual specificity phosphatase 3 (DUSP3) knockdown alleviates acute myocardial infarction damage via inhibiting apoptosis and inflammation. Curr Neurovasc Res. 2023;20:14–22.
Russo LC, Farias JO, Ferruzo PYM, et al. Revisiting the roles of VHR/DUSP3 phosphatase in human diseases. Clinics (Sao Paulo). 2018;73(Suppl 1):e466s.
Alikhan MA, Jones CV, Williams TM, et al. Colony-stimulating factor-1 promotes kidney growth and repair via alteration of macrophage responses. Am J Pathol. 2011;179:1243–1256.
Huen SC, Cantley LG. Macrophage-mediated injury and repair after ischemic kidney injury. Pediatr Nephrol. 2015;30:199–209.
Kezić A, Stajic N, Thaiss F. Innate immune response in kidney ischemia/reperfusion injury: potential target for therapy. J Immunol Res. 2017;2017:6305439.
Slegtenhorst BR, Dor FJ, Rodriguez H, et al. Ischemia/reperfusion injury and its consequences on immunity and inflammation. Curr Transplant Rep. 2014;1:147–154.
Lang R, Raffi FAM. Dual-specificity phosphatases in immunity and infection: an update. Int J Mol Sci. 2019;20:2710.
Yao Z, Zhou G, Wang XS, et al. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem. 1999;274:2118–2125.
Kanellis J, Ma FY, Kandane-Rathnayake R, et al. JNK signalling in human and experimental renal ischaemia/reperfusion injury. Nephrol Dial Transplant. 2010;25:2898–2908.
Jansen MPB, Florquin S, Roelofs JJTH. The role of platelets in acute kidney injury. Nat Rev Nephrol. 2018;14:457–471.
Winkelmayer WC, Finkel KW. Prevention of acute kidney injury using vasoactive or antiplatelet treatment: three strikes and out? JAMA. 2014;312:2221–2222.
Wu H, Uchimura K, Donnelly EL, et al. Comparative analysis and refinement of human PSC-derived kidney organoid differentiation with single-cell transcriptomics. Cell Stem Cell. 2018;23: 869–881.e8.
Wu H, Malone AF, Donnelly EL, et al. Single-cell transcriptomics of a human kidney allograft biopsy specimen defines a diverse inflammatory response. J Am Soc Nephrol. 2018;29:2069–2080.
DeWolf SE, Kasimsetty SG, Hawkes AA, et al. DAMPs released from injured renal tubular epithelial cells activate innate immune signals in healthy renal tubular epithelial cells. Transplantation. 2022;106:1589–1599.
Bou Saba J, Turnquist HR. The reparative roles of IL-33. Transplantation. 2023;107:1069–1078.
Gilbo N, Blondeel J, Pirenne J, et al. Organ repair and regeneration during ex situ dynamic preservation: the future is nano. Transpl Int. 2023;36:11947.
Ramos P, Williams P, Salinas J, et al. Abdominal organ preservation solutions in the age of machine perfusion. Transplantation. 2023;107:326–340.
Shi Z, Tabassum S, Jiang W, et al. Identification of a potent inhibitor of human dual-specific phosphatase, VHR, from computer-aided and NMR-based screening to cellular effects. ChemBioChem. 2007;8:2092–2099.
Wu S, Vossius S, Rahmouni S, et al. Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells. J Med Chem. 2009;52:6716–6723.
