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  1. Article: Prostaglandin E2 receptors as therapeutic targets in renal fibrosis.

    Mutsaers, Henricus A M / Nørregaard, Rikke

    Kidney research and clinical practice

    2022  Volume 41, Issue 1, Page(s) 4–13

    Abstract: Prostaglandin E2 (PGE2), a lipid mediator produced by the cyclooxygenase enzyme system, is the main prostaglandin in the kidney. PGE2 is involved in various physiological and pathophysiological processes in the kidney, including renal hemodynamics, water ...

    Abstract Prostaglandin E2 (PGE2), a lipid mediator produced by the cyclooxygenase enzyme system, is the main prostaglandin in the kidney. PGE2 is involved in various physiological and pathophysiological processes in the kidney, including renal hemodynamics, water and salt balance, and renal fibrosis-a key pathological feature of progressive kidney diseases. PGE2 functions by binding to four G-protein-coupled EP receptors (EP1 to EP4), which stimulate different intracellular signaling pathways. The intrarenal distribution of the four EP receptors as well as the different downstream signaling pathways associated with each receptor give rise to the distinct functional consequence of activating each receptor subtype. This review summarizes the current data on the renal expression of the four EP receptors and delineates the role of each receptor in renal fibrosis.
    Language English
    Publishing date 2022-01-13
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2656420-8
    ISSN 2211-9132
    ISSN 2211-9132
    DOI 10.23876/j.krcp.21.222
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis.

    Nørregaard, Rikke / Mutsaers, Henricus A M / Frøkiær, Jørgen / Kwon, Tae-Hwan

    Physiological reviews

    2023  Volume 103, Issue 4, Page(s) 2827–2872

    Abstract: The kidneys play a key role in maintaining total body homeostasis. The complexity of this task is reflected in the unique architecture of the organ. Ureteral obstruction greatly affects renal physiology by altering hemodynamics, changing glomerular ... ...

    Abstract The kidneys play a key role in maintaining total body homeostasis. The complexity of this task is reflected in the unique architecture of the organ. Ureteral obstruction greatly affects renal physiology by altering hemodynamics, changing glomerular filtration and renal metabolism, and inducing architectural malformations of the kidney parenchyma, most importantly renal fibrosis. Persisting pathological changes lead to chronic kidney disease, which currently affects ∼10% of the global population and is one of the major causes of death worldwide. Studies on the consequences of ureteral obstruction date back to the 1800s. Even today, experimental unilateral ureteral obstruction (UUO) remains the standard model for tubulointerstitial fibrosis. However, the model has certain limitations when it comes to studying tubular injury and repair, as well as a limited potential for human translation. Nevertheless, ureteral obstruction has provided the scientific community with a wealth of knowledge on renal (patho)physiology. With the introduction of advanced omics techniques, the classical UUO model has remained relevant to this day and has been instrumental in understanding renal fibrosis at the molecular, genomic, and cellular levels. This review details key concepts and recent advances in the understanding of obstructive nephropathy, highlighting the pathophysiological hallmarks responsible for the functional and architectural changes induced by ureteral obstruction, with a special emphasis on renal fibrosis.
    MeSH term(s) Humans ; Animals ; Ureteral Obstruction/complications ; Ureteral Obstruction/pathology ; Kidney/metabolism ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/pathology ; Hemodynamics ; Fibrosis ; Disease Models, Animal
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 209902-0
    ISSN 1522-1210 ; 0031-9333
    ISSN (online) 1522-1210
    ISSN 0031-9333
    DOI 10.1152/physrev.00027.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.166: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: The impact of fibrotic diseases on global mortality from 1990 to 2019.

    Mutsaers, Henricus A M / Merrild, Camilla / Nørregaard, Rikke / Plana-Ripoll, Oleguer

    Journal of translational medicine

    2023  Volume 21, Issue 1, Page(s) 818

    MeSH term(s) Humans ; Fibrosis ; Mortality ; Global Health
    Language English
    Publishing date 2023-11-16
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/s12967-023-04690-7
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  4. Article: Editorial: Organ Fibrosis: Pathogenesis, Biomarkers and Therapeutic Targets.

    Mutsaers, Henricus A M / Nørregaard, Rikke / Olinga, Peter

    Frontiers in medicine

    2021  Volume 8, Page(s) 793507

    Language English
    Publishing date 2021-11-05
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.793507
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  5. Article ; Online: Standardized Protocol for the Preparation of Precision-Cut Kidney Slices: A Translational Model of Renal Fibrosis.

    Jensen, Michael Schou / Merrild, Camilla / Nørregaard, Rikke / Olinga, Peter / Mutsaers, Henricus A M

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2664, Page(s) 123–134

    Abstract: Renal fibrosis is a hallmark of progressive renal diseases. To date, there is a lack of effective therapeutics for the treatment of renal fibrosis, in part due to the scarcity of clinically relevant translational disease models. Since the early 1920s, ... ...

    Abstract Renal fibrosis is a hallmark of progressive renal diseases. To date, there is a lack of effective therapeutics for the treatment of renal fibrosis, in part due to the scarcity of clinically relevant translational disease models. Since the early 1920s, hand-cut tissue slices have been used as a means to better understand organ (patho)physiology in a variety of scientific fields. From that time, the equipment and methodology for the preparation of tissue slices has continuously improved, thereby expanding the applicability of the model. Nowadays, precision-cut kidney slices (PCKS) have been demonstrated to be an extremely valuable translation model for renal (patho)physiology, bridging the gap between preclinical and clinical research. A key feature of PCKS is that the slices contain all cell types and acellular components of the whole organ in the original configuration while preserving cell-cell and cell-matrix interactions. In this chapter, we describe how to prepare PCKS and how the model can be implemented in fibrosis research.
    MeSH term(s) Humans ; Kidney/metabolism ; Kidney Diseases/metabolism ; Fibrosis
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3179-9_9
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  6. Article ; Online: Transcutaneous measurement of renal function in two rodent models of obstructive nephropathy.

    Jensen, Michael Schou / de Araujo, Isabela Bastos Binotti Abreu / Mutsaers, Henricus A M / Nørregaard, Rikke

    BMC research notes

    2023  Volume 16, Issue 1, Page(s) 119

    Abstract: Objective: Glomerular filtration rate (GFR) is a key indicator of renal function. In both clinical practice and pre-clinical research, serum levels of endogenous filtration markers, such as creatinine, are often used to estimate GFR. However, these ... ...

    Abstract Objective: Glomerular filtration rate (GFR) is a key indicator of renal function. In both clinical practice and pre-clinical research, serum levels of endogenous filtration markers, such as creatinine, are often used to estimate GFR. However, these markers often do not reflect minor changes in renal function. In this study, we therefore set out to evaluate the applicability of transcutaneous GFR (tGFR) measurements to monitor the changes in renal function, as compared to plasma creatinine (pCreatinine), in two models of obstructive nephropathy, namely unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction followed by release (BUO-R) in male Wistar rats.
    Results: UUO animals showed a significant reduction in tGFR compared to baseline; whereas pCreatinine levels were not significantly changed. In BUO animals, tGFR drops 24 h post BUO and remains lower upon release of the obstruction until day 11. Concomitantly, pCreatinine levels were also increased 24 h after obstruction and 24 h post release, however after 4 days, pCreatinine returned to baseline levels. In conclusion, this study revealed that the tGFR method is superior at detecting minor changes in renal function as compared to pCreatinine measurements.
    MeSH term(s) Rats ; Animals ; Male ; Kidney/physiology ; Ureteral Obstruction ; Rodentia ; Creatinine ; Rats, Wistar ; Kidney Diseases ; Glomerular Filtration Rate
    Chemical Substances Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2413336-X
    ISSN 1756-0500 ; 1756-0500
    ISSN (online) 1756-0500
    ISSN 1756-0500
    DOI 10.1186/s13104-023-06387-y
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  7. Article ; Online: Editorial

    Henricus A. M. Mutsaers / Rikke Nørregaard / Peter Olinga

    Frontiers in Medicine, Vol

    Organ Fibrosis: Pathogenesis, Biomarkers and Therapeutic Targets

    2021  Volume 8

    Keywords fibrosis ; chronic kidney disease ; non-alcoholic fatty liver disease ; cirrhosis ; pulmonary fibrosis ; renal fibrosis ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight.

    Monti, Giulia / Gomes Moreira, Diana / Richner, Mette / Mutsaers, Henricus Antonius Maria / Ferreira, Nelson / Jan, Asad

    Cells

    2022  Volume 11, Issue 13

    Abstract: Defects in brain energy metabolism and proteopathic stress are implicated in age-related degenerative neuronopathies, exemplified by Alzheimer's disease (AD) and Parkinson's disease (PD). As the currently available drug regimens largely aim to mitigate ... ...

    Abstract Defects in brain energy metabolism and proteopathic stress are implicated in age-related degenerative neuronopathies, exemplified by Alzheimer's disease (AD) and Parkinson's disease (PD). As the currently available drug regimens largely aim to mitigate cognitive decline and/or motor symptoms, there is a dire need for mechanism-based therapies that can be used to improve neuronal function and potentially slow down the underlying disease processes. In this context, a new class of pharmacological agents that achieve improved glycaemic control via the glucagon-like peptide 1 (GLP-1) receptor has attracted significant attention as putative neuroprotective agents. The experimental evidence supporting their potential therapeutic value, mainly derived from cellular and animal models of AD and PD, has been discussed in several research reports and review opinions recently. In this review article, we discuss the pathological relevance of derangements in the neurovascular unit and the significance of neuron-glia metabolic coupling in AD and PD. With this context, we also discuss some unresolved questions with regard to the potential benefits of GLP-1 agonists on the neurovascular unit (NVU), and provide examples of novel experimental paradigms that could be useful in improving our understanding regarding the neuroprotective mode of action associated with these agents.
    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Animals ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Parkinson Disease/metabolism
    Chemical Substances Glucagon-Like Peptide-1 Receptor ; Neuroprotective Agents ; Glucagon-Like Peptide 1 (89750-14-1)
    Language English
    Publishing date 2022-06-25
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11132023
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  9. Article ; Online: An animal-free preclinical drug screening platform based on human precision-cut kidney slices.

    Mutsaers, Henricus A M / Jensen, Michael Schou / Kresse, Jean-Claude / Tingskov, Stine Julie / Madsen, Mia Gebauer / Nørregaard, Rikke

    BMC research notes

    2023  Volume 16, Issue 1, Page(s) 39

    Abstract: Objective: Renal fibrosis is one of the main pathophysiological processes underlying the progression of chronic kidney disease and kidney allograft failure. In the past decades, overwhelming efforts have been undertaken to find druggable targets for the ...

    Abstract Objective: Renal fibrosis is one of the main pathophysiological processes underlying the progression of chronic kidney disease and kidney allograft failure. In the past decades, overwhelming efforts have been undertaken to find druggable targets for the treatment of renal fibrosis, mainly using cell- and animal models. However, the latter often do not adequately reflect human pathogenesis, obtained results differ per strain within a given species, and the models are associated with considerable discomfort for the animals. Therefore, the objective of this study is to implement the 3Rs in renal fibrosis research by establishing an animal-free drug screening platform for renal fibrosis based on human precision-cut kidney slices (PCKS) and by limiting the use of reagents that are associated with significant animal welfare concerns.
    Results: Using Western blotting and gene expression arrays, we show that transforming growth factor-β (TGF-β) induced fibrosis in human PCKS. In addition, our results demonstrated that butaprost, SC-19220 and tamoxifen - all putative anti-fibrotic compounds - altered TGF-β-induced pro-fibrotic gene expression in human PCKS. Moreover, we observed that all compounds modulated fairly distinct sets of genes, however they all impacted TGF-β/SMAD signaling. In conclusion, this study revealed that it is feasible to use an animal-free approach to test drug efficacy and elucidate mechanisms of action.
    MeSH term(s) Animals ; Humans ; Drug Evaluation, Preclinical/methods ; Fibrosis ; Kidney/pathology ; Kidney Diseases/drug therapy ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta/genetics ; Animal Testing Alternatives
    Chemical Substances Transforming Growth Factor beta
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2413336-X
    ISSN 1756-0500 ; 1756-0500
    ISSN (online) 1756-0500
    ISSN 1756-0500
    DOI 10.1186/s13104-023-06303-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Murine Precision-Cut Kidney Slices as an

    Stribos, Elisabeth G D / Seelen, Marc A / van Goor, Harry / Olinga, Peter / Mutsaers, Henricus A M

    Frontiers in physiology

    2017  Volume 8, Page(s) 1026

    Abstract: Renal fibrosis is characterized by progressive accumulation of extracellular matrix (ECM) proteins, resulting in loss of organ function and eventually requiring renal replacement therapy. Unfortunately, no efficacious treatment options are available to ... ...

    Abstract Renal fibrosis is characterized by progressive accumulation of extracellular matrix (ECM) proteins, resulting in loss of organ function and eventually requiring renal replacement therapy. Unfortunately, no efficacious treatment options are available to halt renal fibrosis and translational models to test pharmacological agents are not always representative. Here, we evaluated murine precision-cut kidney slices (mPCKS) as a promising
    Language English
    Publishing date 2017-12-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2017.01026
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