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  1. Article ; Online: Traveling to the left: A story of PKD1L1-containing vesicles.

    Tran, Uyen / Wessely, Oliver

    Developmental cell

    2023  Volume 58, Issue 16, Page(s) 1445–1446

    Abstract: The establishment of the left-right asymmetry in vertebrate animals is orchestrated by a series of tightly regulated events. In this issue of Developmental Cell, Tanaka et al. provide a tantalizing model to show how fluid flow in the mouse ventral node ... ...

    Abstract The establishment of the left-right asymmetry in vertebrate animals is orchestrated by a series of tightly regulated events. In this issue of Developmental Cell, Tanaka et al. provide a tantalizing model to show how fluid flow in the mouse ventral node becomes integrated in a molecular cellular signature of asymmetry.
    MeSH term(s) Animals ; Mice
    Language English
    Publishing date 2023-08-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2023.07.016
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    Zs.A 5742: Show issues Location:
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  2. Article ; Online: GSKβ as a target in podocyte aging.

    Shankland, Stuart J / Wessely, Oliver

    Kidney international

    2022  Volume 102, Issue 3, Page(s) 463–465

    MeSH term(s) Aging ; Glomerulosclerosis, Focal Segmental ; Humans ; Kidney Glomerulus ; Podocytes
    Language English
    Publishing date 2022-06-01
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.04.041
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    Zs.A 797: Show issues Location:
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  3. Article ; Online: Zoning in on podocytes.

    Shankland, Stuart J / Wessely, Oliver

    Kidney international

    2022  Volume 102, Issue 5, Page(s) 966–968

    Abstract: Podocytes undergo defined morphologic changes during development, homeostasis, and aging, and on injury. Quantitative podometric assessments of podocyte endowment provide a powerful tool to interrogate glomerular health. Expanding this approach to a ... ...

    Abstract Podocytes undergo defined morphologic changes during development, homeostasis, and aging, and on injury. Quantitative podometric assessments of podocyte endowment provide a powerful tool to interrogate glomerular health. Expanding this approach to a regional assessment demonstrates that the podocytes from cortical, subcortical, and juxtamedullary glomeruli are not only morphologically heterogeneous per se, but respond differently to stressors, such as age and hypertension. This suggests that zonal glomerular changes harbor critical information to understand glomerulopathies.
    MeSH term(s) Humans ; Podocytes ; Kidney Glomerulus ; Kidney Diseases ; Hypertension
    Language English
    Publishing date 2022-10-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.08.030
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  4. Article ; Online: The proliferative and the antifibrotic side of PAX2 in tubular repair.

    Wessely, Oliver / Shankland, Stuart J

    Kidney international

    2022  Volume 102, Issue 1, Page(s) 12–13

    Abstract: Regenerative repair following injury to proximal tubular epithelial cells (PTECs) is essential to restore the kidney to normal function in acute kidney injury. Failure to accomplish this leads to chronic kidney disease. Expression of the paired-box ... ...

    Abstract Regenerative repair following injury to proximal tubular epithelial cells (PTECs) is essential to restore the kidney to normal function in acute kidney injury. Failure to accomplish this leads to chronic kidney disease. Expression of the paired-box transcription factor Pax2 in PTECs is required for their regenerative proliferation and repair. However, a loss-of-function study now shows that the absence of Pax2 not only impacts PTEC proliferation but also causes myofibroblast recruitment leading to excessive tubulointerstitial fibrosis.
    MeSH term(s) Acute Kidney Injury/pathology ; Animals ; Epithelial Cells/metabolism ; Fibrosis ; Kidney/metabolism ; Kidney Tubules, Proximal/pathology ; PAX2 Transcription Factor/genetics ; PAX2 Transcription Factor/metabolism
    Chemical Substances PAX2 Transcription Factor
    Language English
    Publishing date 2022-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.04.016
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  5. Article ; Online: Repurposing drugs for diseases associated with podocyte dysfunction.

    Shankland, Stuart J / Jefferson, J Ashley / Wessely, Oliver

    Kidney international

    2023  Volume 104, Issue 3, Page(s) 455–462

    Abstract: The majority of podocyte disorders are progressive in nature leading to chronic kidney disease and often kidney failure. The scope of current therapies is typically nonspecific immunosuppressant medications, which are accompanied by unwanted and serious ... ...

    Abstract The majority of podocyte disorders are progressive in nature leading to chronic kidney disease and often kidney failure. The scope of current therapies is typically nonspecific immunosuppressant medications, which are accompanied by unwanted and serious side effects. However, many exciting clinical trials are underway to reduce the burden of podocyte diseases in our patients. Major advances and discoveries have recently been made experimentally in our understanding of the molecular and cellular mechanisms underlying podocyte injury in disease. This begs the question of how best to take advantage of these impressive strides. One approach to consider is the repurposing of therapeutics that have already been approved by the Food and Drug Administration, European Medicines Agency, and other regulatory agencies for indications beyond the kidney. The advantages of therapy repurposing include known safety profiles, drug development that has already been completed, and overall reduced costs for studying alternative indications for selected therapies. The purpose of this mini review is to examine the experimental literature of podocyte damage and determine if there are mechanistic targets in which prior approved therapies can be considered for repurposing to podocyte disorders.
    MeSH term(s) Humans ; Podocytes ; Pharmaceutical Preparations ; Drug Repositioning ; Kidney ; Renal Insufficiency, Chronic/drug therapy
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2023.05.018
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  6. Article ; Online: Does treating with anti-PD-1 to improve glomerular health come without a cost? Reply.

    Shankland, Stuart J / Pippin, Jeffrey W / Wessely, Oliver

    The Journal of clinical investigation

    2022  Volume 132, Issue 22

    MeSH term(s) Programmed Cell Death 1 Receptor ; B7-H1 Antigen
    Chemical Substances Programmed Cell Death 1 Receptor ; B7-H1 Antigen
    Language English
    Publishing date 2022-11-15
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI165287
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  7. Article ; Online: Does treating with anti–PD-1 to improve glomerular health come without a cost? Reply.

    Stuart J. Shankland / Jeffrey W. Pippin / Oliver Wessely

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 22

    Keywords Aging ; Medicine ; R
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Podocyte Senescence and Aging.

    Shankland, Stuart J / Rule, Andrew D / Kutz, J Nathan / Pippin, Jeffrey W / Wessely, Oliver

    Kidney360

    2023  Volume 4, Issue 12, Page(s) 1784–1793

    Abstract: As the population in many industrial countries is aging, the risk, incidence, and prevalence of CKD increases. In the kidney, advancing age results in a progressive decrease in nephron number and an increase in glomerulosclerosis. In this review, we ... ...

    Abstract As the population in many industrial countries is aging, the risk, incidence, and prevalence of CKD increases. In the kidney, advancing age results in a progressive decrease in nephron number and an increase in glomerulosclerosis. In this review, we focus on the effect of aging on glomerular podocytes, the post-mitotic epithelial cells critical for the normal integrity and function of the glomerular filtration barrier. The podocytes undergo senescence and transition to a senescence-associated secretory phenotype typified by the production and secretion of inflammatory cytokines that can influence neighboring glomerular cells by paracrine signaling. In addition to senescence, the aging podocyte phenotype is characterized by ultrastructural and functional changes; hypertrophy; cellular, oxidative, and endoplasmic reticulum stress; reduced autophagy; and increased expression of aging genes. This results in a reduced podocyte health span and a shortened life span. Importantly, these changes in the pathways/processes characteristic of healthy podocyte aging are also often similar to pathways in the disease-induced injured podocyte. Finally, the better understanding of podocyte aging and senescence opens therapeutic options to slow the rate of podocyte aging and promote kidney health.
    MeSH term(s) Humans ; Podocytes/metabolism ; Aging/metabolism ; Kidney Glomerulus/metabolism ; Kidney Diseases/metabolism ; Epithelial Cells
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0000000000000284
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  9. Article ; Online: Podocytes from hypertensive and obese mice acquire an inflammatory, senescent, and aged phenotype.

    McKinzie, Sierra R / Kaverina, Natalya / Schweickart, Robert Allen / Chaney, Christopher P / Eng, Diana G / Pereira, Beatriz Maria Veloso / Kestenbaum, Bryan / Pippin, Jeffrey W / Wessely, Oliver / Shankland, Stuart J

    American journal of physiology. Renal physiology

    2024  Volume 326, Issue 4, Page(s) F644–F660

    Abstract: Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or ... ...

    Abstract Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA sequencing of isolated podocytes from experimental models and their respective controls. Key findings were validated by immunostaining. In addition to a decrease in canonical proteins and reduced podocyte number, podocytes from both hypertensive and obese mice exhibited a sterile inflammatory phenotype characterized by increases in NLR family pyrin domain containing 3 (NLRP3) inflammasome, protein cell death-1, and Toll-like receptor pathways. Finally, although the mice were young, podocytes in both models exhibited increased expression of senescence and aging genes, including genes consistent with a senescence-associated secretory phenotype. However, there were differences between the hypertension- and obesity-associated senescence phenotypes. Both show stress-induced podocyte senescence characterized by increased
    MeSH term(s) Humans ; Mice ; Animals ; Aged ; Podocytes/metabolism ; Mice, Obese ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Inflammasomes/metabolism ; Phenotype ; Kidney Diseases/metabolism ; Obesity/metabolism ; Hypertension/genetics ; Hypertension/metabolism ; Desoxycorticosterone ; Acetates/metabolism ; RNA, Messenger/metabolism
    Chemical Substances NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes ; Desoxycorticosterone (40GP35YQ49) ; Acetates ; RNA, Messenger
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00417.2023
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    Uc I Zs.89: Show issues Location:
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  10. Article ; Online: Podocyte Aging: Why and How Getting Old Matters.

    Shankland, Stuart J / Wang, Yuliang / Shaw, Andrey S / Vaughan, Joshua C / Pippin, Jeffrey W / Wessely, Oliver

    Journal of the American Society of Nephrology : JASN

    2021  Volume 32, Issue 11, Page(s) 2697–2713

    Abstract: The effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population's increasing longevity. Age-associated changes to podocytes, which are terminally differentiated ... ...

    Abstract The effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population's increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.
    MeSH term(s) Adult ; Aged ; Aging/physiology ; Animals ; Autophagy ; Caloric Restriction ; Cell Cycle ; Cell Shape ; Cells, Cultured ; Cellular Senescence ; DNA Damage ; Female ; Gene Expression ; Humans ; Inflammasomes ; Kidney Glomerulus/cytology ; Kidney Glomerulus/growth & development ; Male ; Mice ; Middle Aged ; Mitochondria/metabolism ; Models, Animal ; Oligopeptides/pharmacology ; Oxidative Stress ; Podocytes/cytology ; Podocytes/metabolism ; Rats ; Regulated Cell Death ; Sirtuins/metabolism ; Species Specificity ; Young Adult
    Chemical Substances Inflammasomes ; Oligopeptides ; arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide ; Sirtuins (EC 3.5.1.-)
    Language English
    Publishing date 2021-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2021050614
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    Zs.A 3344: Show issues Location:
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