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  1. Article ; Online: The Dual-specificity Phosphatase 3 (DUSP3): A Potential Target Against Renal Ischemia/Reperfusion Injury.

    Khbouz, Badr / Musumeci, Lucia / Grahammer, Florian / Jouret, François

    Transplantation

    2024  

    Abstract: 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/ ...

    Abstract 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.
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000005009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Radiotherapy Advances in Renal Disease-Focus on Renal Ischemic Preconditioning.

    Khbouz, Badr / Gu, Shiyang / Pinto Coelho, Tiago / Lallemand, François / Jouret, François

    Bioengineering (Basel, Switzerland)

    2023  Volume 10, Issue 1

    Abstract: Ionizing irradiation is widely applied as a fundamental therapeutic treatment in several diseases. Acute kidney injury (AKI) represents a global public health problem with major morbidity and mortality. Renal ischemia/reperfusion (I/R) is the main cause ... ...

    Abstract Ionizing irradiation is widely applied as a fundamental therapeutic treatment in several diseases. Acute kidney injury (AKI) represents a global public health problem with major morbidity and mortality. Renal ischemia/reperfusion (I/R) is the main cause of AKI. I/R injury occurs when blood flow to the kidney is transiently interrupted and then restored. Such an ischemic insult significantly impairs renal function in the short and long terms. Renal ischemic preconditioning (IPC) corresponds to the maneuvers intended to prevent or attenuate the ischemic damage. In murine models, irradiation-induced preconditioning (IP) renders the renal parenchyma resistant to subsequent damage by activating defense pathways involved in oxidative stress, angiogenesis, and inflammation. Before envisioning translational applications in patients, safe irradiation modalities, including timing, dosage, and fractionation, need to be defined.
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering10010068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse.

    Khbouz, Badr / Rowart, Pascal / Poma, Laurence / Dahlke, Eileen / Bottner, Martina / Stokes, Matthew / Bolen, Géraldine / Rahmouni, Souad / Theilig, Franziska / Jouret, François

    Acta physiologica (Oxford, England)

    2021  Volume 234, Issue 2, Page(s) e13735

    Abstract: 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 ischaemia/reperfusion (I/R). We postulate that the ... ...

    Abstract 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 ischaemia/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
    Results: At baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31-positive vascular network was significantly larger in Dusp3
    Conclusion: Genetic inactivation of Dusp3 is associated with kidney conditioning against I/R, possibly due to attenuated inflammation and improved perfusion.
    MeSH term(s) Acute Kidney Injury/metabolism ; Animals ; Dual Specificity Phosphatase 3/genetics ; Endothelial Cells/metabolism ; Inflammation/genetics ; Inflammation/metabolism ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury/genetics ; Reperfusion Injury/metabolism
    Chemical Substances Dual Specificity Phosphatase 3 (EC 3.1.3.48) ; Dusp3 protein, mouse (EC 3.1.3.48)
    Language English
    Publishing date 2021-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13735
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Kidney-targeted irradiation triggers renal ischemic preconditioning in mice.

    Khbouz, Badr / Lallemand, François / Cirillo, Arianna / Rowart, Pascal / Legouis, David / Sounni, Nor Eddine / Noël, Agnès / De Tullio, Pascal / de Seigneux, Sophie / Jouret, François

    American journal of physiology. Renal physiology

    2022  Volume 323, Issue 2, Page(s) F198–F211

    Abstract: Renal ischemia-reperfusion (I/R) causes acute kidney injury (AKI). Ischemic preconditioning (IPC) attenuates I/R-associated AKI. Whole body irradiation induces renal IPC in mice. Still, the mechanisms remain largely unknown. Furthermore, the impact of ... ...

    Abstract Renal ischemia-reperfusion (I/R) causes acute kidney injury (AKI). Ischemic preconditioning (IPC) attenuates I/R-associated AKI. Whole body irradiation induces renal IPC in mice. Still, the mechanisms remain largely unknown. Furthermore, the impact of kidney-centered irradiation on renal resistance against I/R has not been studied. Renal irradiation (8.5 Gy) was done in male 8- to 12-wk-old C57bl/6 mice using a small animal radiation therapy device. Left renal I/R was performed by clamping the renal pedicles for 30 min, with simultaneous right nephrectomy, at 7, 14, and 28 days postirradiation. The renal reperfusion lasted 48 h. Following I/R, blood urea nitrogen (BUN) and serum creatinine (SCr) levels were lower in preirradiated mice compared with controls; so was the histological Jablonski score of AKI. The metabolomics signature of renal I/R was attenuated in preirradiated mice. The numbers of proliferating cell nuclear antigen (PCNA)-, cluster of differentiation molecule 11b (CD11b)-, and cell surface glycoprotein F4/80-positive cells in the renal parenchyma post-I/R were reduced in preirradiated versus control groups. Such IPC was significantly observed as early as
    MeSH term(s) Acute Kidney Injury/etiology ; Acute Kidney Injury/pathology ; Acute Kidney Injury/prevention & control ; Animals ; Ischemia/metabolism ; Ischemic Preconditioning ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury/pathology ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2022-07-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00005.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Role for the membrane estrogen receptor alpha in the sexual differentiation of the brain.

    Khbouz, Badr / de Bournonville, Catherine / Court, Lucas / Taziaux, Mélanie / Corona, Rebeca / Arnal, Jean-François / Lenfant, Françoise / Cornil, Charlotte A

    The European journal of neuroscience

    2019  Volume 52, Issue 1, Page(s) 2627–2645

    Abstract: Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best-characterized responses activated by estrogens in adulthood and largely depend on ERα. ... ...

    Abstract Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best-characterized responses activated by estrogens in adulthood and largely depend on ERα. Evidence exists that nucleus- and membrane-initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both in short- and long-term. However, questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated responses. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site, which prevents membrane ERα signaling (mERα; ERα-C451A), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no genotype effect on the expression of female sexual behavior, while male sexual behavior was significantly reduced, but not abolished, in males homozygous for the mutation. Similarly, the number of kisspeptin- (Kp-ir) and calbindin-immunoreactive (Cb-ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually dimorphic nucleus of the preoptic area (SDN-POA), respectively, were not different between genotypes in females. In contrast, homozygous males showed increased numbers of Kp-ir and decreased numbers of Cb-ir neurons compared to wild-types, thus leading to an intermediate phenotype between females and wild-type males. Importantly, females neonatally treated with estrogens exhibited the same neurochemical phenotype as their corresponding genotype among males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain.
    MeSH term(s) Animals ; Brain/metabolism ; Calbindins ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Female ; Male ; Mice ; Pregnancy ; Preoptic Area/metabolism ; Sex Characteristics ; Sex Differentiation
    Chemical Substances Calbindins ; Estrogen Receptor alpha
    Language English
    Publishing date 2019-12-30
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.14646
    Database MEDical Literature Analysis and Retrieval System OnLINE

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