The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage following ischemia/reperfusion injury in mouse

Khbouz, Badr; Rowart, Pascal; POMA, Laurence; Dahlke, Eileen; Bottner, Martina; Matt, Stokes; Bolen, Geraldine; Rahmouni, Souad; Theilig, Franziska; JOURET, François

doi:10.1111/apha.13735

Article (Scientific journals)

The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage following ischemia/reperfusion injury in mouse

Khbouz, Badr; Rowart, Pascal; POMA, Laurence et al.

2021 • In Acta Physiologica

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/264598

DOI
10.1111/apha.13735

PubMed
34704357

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Keywords :

ischemia-reperfusion; DUSP3; preconditionning; renal physiology; inflammation; angiogenesis

Abstract :

[en] Aim: Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response, with a putative role in angiogenesis. Modulating inflammation and perfusion contributes to renal conditioning against ischemia/reperfusion (I/R). We postulate that the functional loss of DUSP3 is associated with kidney resistance to I/R. Methods: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal I/R (30min/48h). Renal injury was assessed based on serum levels of urea (BUN) and Jablonski score. The expression of CD31 and VEGF vascular markers was quantified by RT-qPCR and immuno-staining. Renal resistivity index (RRI) was measured in vivo by Doppler ultrasound. Comparative phosphoproteomics was conducted using IMAC enrichment of phosphopeptides. Inflammatory markers were quantified at both mRNA and protein levels in ischemic vs. non-ischemic kidneys in WT versus Dusp3-/- . Results: At baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31-positive vascular network was significantly larger in Dusp3-/- kidneys compared to WT, with a lower RRI in Dusp3-/- mice. Following I/R, BUN and Jablonski score were significantly lower in Dusp3-/- vs. WT mice. Phosphoproteomics highlighted a down-regulation of inflammatory pathways and up-regulation of phospho-sites involved in cell metabolism and VEGF-related angiogenesis in Dusp3-/- vs. WT ischemic kidneys. Dusp3-/- ischemic kidneys showed decreased mRNA levels of CD11b, TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-positive cells were reduced in Dusp3-/- vs. WT kidneys post I/R. Conclusion: Genetic inactivation of Dusp3 is associated with kidney conditioning against I/R, possibly due to attenuated inflammation and improved perfusion.

Research center :

GIGA‐R - Giga‐Research - ULiège

Disciplines :

Urology & nephrology

Author, co-author :

Khbouz, Badr ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie

Rowart, Pascal

POMA, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie

Dahlke, Eileen

Bottner, Martina

Matt, Stokes

Bolen, Geraldine

Rahmouni, Souad ; Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics

Theilig, Franziska

JOURET, François ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de néphrologie

Language :

English

Title :

The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage following ischemia/reperfusion injury in mouse

Publication date :

27 October 2021

Journal title :

Acta Physiologica

ISSN :

1748-1708

eISSN :

1748-1716

Publisher :

Wiley, Oxford, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

Rôle de DUSP3 dans l'ischémie rénale chez la souris

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
Fonds Léon Fredericq [BE]

Available on ORBi :

since 29 October 2021

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Bibliography

Hoste EA, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14:607-625.
Bonventre JJV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Investig. 2011;121:4210-4221.
Rowart P, Erpicum P, Detry O, et al. Mesenchymal stromal cell therapy in ischemia/reperfusion injury. J Immunol Res. 2015;2015:1-8.
Erpicum P, Rowart P, Poma L, Krzesinski J-M, Detry O, Jouret F. 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.
Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317.
Shen H, Kreisel D, Goldstein DR. Processes of sterile inflammation. J Immunol. 2013;191:2857-2863.
Kvietys PR, Granger DN. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med. 2012;52:556-592.
Denecke C, Tullius SG. Innate and adaptive immune responses subsequent to ischemia-reperfusion injury in the kidney. Progrès En Urologie. 2014;24:S13-S19.
Chiba T, Cerqueira DM, Li Y, et al. Endothelial-derived miR-17∼92 promotes angiogenesis to protect against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2021;32:553-562.
Wang Y, Mi Y, Tian J, et al. Intermedin alleviates renal ischemia-reperfusion injury and enhances neovascularization in Wistar rats. Drug Des Devel Ther. 2020;14:4825-4834.
Erpicum P, Detry O, Weekers L, et al. Mesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion. Nephrol Dial Transplant. 2014;29:1487-1493.
Wever KE, Menting TP, Rovers M, et al. Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis. PLoS One. 2012;7:e32296.
Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM. Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein phosphatase. Biochemistry. 2002;41:3009-3017.
Huang C-Y, Tan T-H. DUSPs, to MAP kinases and beyond. Cell Biosci. 2012;2:24.
Ishibashi T, Bottaro DP, Chan A, Miki T, Aaronson SA. Expression cloning of a human dual-specificity phosphatase. Proc Natl Acad Sci USA. 1992;89:12170-12174.
Pavic K, Duan G, Köhn M. VHR/DUSP3 phosphatase: structure, function and regulation. FEBS J. 2015;282:1871-1890.
Alonso A, Saxena M, Williams S, Mustelin T. Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation. J Biol Chem. 2001;276:4766-4771.
Amand M, Erpicum C, Bajou K, et al. DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase. Mol Cancer. 2014;13:1-18.
Singh P, Dejager L, Amand M, et al. DUSP3 genetic deletion confers M2-like macrophage-dependent tolerance to septic shock. J Imunol. 2015;194:4951-4962.
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.
Khajavi M, Zhou Y, Schiffer AJ, et al. Identification of Basp1 as a novel angiogenesis-regulating gene by multi-model system studies. FASEB J. 2021;35:e21404.
Cho C, Wang Y, Smallwood PM, et al. Dlg1 activates beta-catenin signaling to regulate retinal angiogenesis and the blood-retina and blood-brain barriers. Elife. 2019;8:e45542.
Cappellini E, Vanetti C, Vicentini LM, et al. Silencing of Eps8 inhibits in vitro angiogenesis. Life Sci. 2015;131:30-36.
Hernández-García R, Iruela-Arispe ML, Reyes-Cruz G, et al. Endothelial RhoGEFs: a systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells. Vascul Pharmacol. 2015;74:60-72.
Wang H, Ramshekar A, Kunz E, et al. IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation. Angiogenesis. 2020;23:685-698.
Liu H, Qiu Y, Pei X, et al. Endothelial specific YY1 deletion restricts tumor angiogenesis and tumor growth. Sci Rep. 2020;10:20493.
Hu F, Sun X, Li G, et al. Inhibition of SIRT2 limits tumour angiogenesis via inactivation of the STAT3/VEGFA signalling pathway. Cell Death Dis. 2018;10:9.
Kiso M, Tanaka S, Saji S, et al. Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network. Int J Cancer. 2018;143:2905-2918.
Watari K, Shibata T, Fujita H, et al. NDRG1 activates VEGF-A-induced angiogenesis through PLCγ1/ERK signaling in mouse vascular endothelial cells. Commun Biol. 2020;3:107.
Erpicum P, Rowart P, Defraigne J-O, Krzesinski J-M, Jouret F. What we need to know about lipid-associated injury in case of renal ischemia-reperfusion. Am J Physiol Renal Physiol. 2018;315(6):F1714-F1719.
Yañez AJ, Ludwig HC, Bertinat R, et al. Different involvement for aldolase isoenzymes in kidney glucose metabolism: aldolase B but not aldolase A colocalizes and forms a complex with FBPase. J Cell Physiol. 2005;202:743-753.
Sharma R, Sanchez-Ferras O, Bouchard M. Pax genes in renal development, disease and regeneration. Semin Cell Dev Biol. 2015;44:97-106.
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.
Kaushal GP, Shah SV. Challenges and advances in the treatment of AKI. J Am Soc Nephrol. 2014;25:877-883.
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.
Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62:237-244.
Tian L, Shao X, Xie Y, et al. Kidney injury molecule-1 is elevated in nephropathy and mediates macrophage activation via the Mapk signalling pathway. Cell Physiol Biochem. 2017;41:769-783.
Jongstra-Bilen J, Jongstra J. Leukocyte-specific protein 1 (LSP1): a regulator of leukocyte emigration in inflammation. Immunol Res. 2006;35:65-74.
Yang X, Qi F, Wei S, et al. The transcription factor C/EBPβ promotes HFL-1 cell migration, proliferation, and inflammation by activating lncRNA HAS2-AS1 in hypoxia. Front Cell Dev Biol. 2021;9:651913.
Tögel FE, Westenfelder C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol. 2010;6:179-183.
Russo LC, Farias JO, Ferruzo PYM, Monteiro LF, Forti FL. Revisiting the roles of VHR/DUSP3 phosphatase in human diseases. Clinics. 2018;73:1-7.
Monteiro LF, Ferruzo PYM, Russo LC, Farias JO, Forti FL. DUSP3/VHR: a druggable dual phosphatase for human diseases. Rev Physiol Biochem Pharmacol. 2019;176:1-35.
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 Imunol Res. 2017;2017:1-10.
Slegtenhorst BR, Dor FJ, Rodriguez H, Voskuil FJ, Tullius SG. 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(11):2710.
Pallet N, Thervet E, Timsit M-O. Angiogenic response following renal ischemia reperfusion injury: new players. Prog Urol. 2014;24:S20–S25. 10.1016/S1166-7087(14)70059-4
Vandereyken M, Jacques S, Van OE, et al. Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner. PLoS One. 2017;1(1-23):21.
Faucher Q, Alarcan H, Marquet P, Barin-Le GC. Effects of ischemia-reperfusion on tubular cell membrane transporters and consequences in kidney transplantation. J Clin Med. 2020;9:2610.
Grahammer F, Ramakrishnan SK, Rinschen MM, et al. mTOR regulates endocytosis and nutrient transport in proximal tubular cells. J Am Soc Nephrol. 2017;28:230-241.
Juszczak F, Caron N, Mathew AV, Declèves AE. Critical role for AMPK in metabolic disease-induced chronic kidney disease. Int J Mol Sci. 2020;21:7994.
Legouis D, Ricksten SE, Faivre A, et al. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nat Metab. 2020;2:732-743.
Fan Y, Elyce O, Frank Y, et al. c-Jun Amino Terminal Kinase Signaling Promotes Aristolochic Acid-Induced Acute Kidney Injury. Front Physiol. 2021;12: 599114.
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 vacciniaH1-related (VHR) phosphatase decrease proliferation of cervix cancer cells. J Med Chem. 2009;52:6716-6723.
Stokes MP, Farnsworth CL, Gu H, et al. Complementary PTM profiling of drug response in human gastric carcinoma by immunoaffinity and IMAC methods with total proteome analysis. Proteomes. 2015;3:160-183.
Possemato AP, Paulo JA, Mulhern D, et al. Multiplexed phosphoproteomic profiling using titanium dioxide and immunoaffinity enrichments reveals complementary phosphorylation events. J Proteome Res. 2017;16:1506-1514.
Olsen JV, de Godoy LM, Li G, et al. Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol Cell Proteomics. 2005;4:2010-2021.
Huttlin EL, Jedrychowski MP, Elias JE, et al. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010;143:1174-1189.
MacLean B, Tomazela DM, Shulman N, et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics. 2010;26:966-968.
O'Shea JP, Chou MF, Quader SA, et al. pLogo: a probabilistic approach to visualizing sequence motifs. Nat Methods. 2013;10:1211-1212.