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  1. 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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  2. 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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  3. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Parietal epithelial cell differentiation to a podocyte fate in the aged mouse kidney.

    Kaverina, Natalya V / Eng, Diana G / Miner, Jeffrey H / Pippin, Jeffrey W / Shankland, Stuart J

    Aging

    2020  Volume 12, Issue 17, Page(s) 17601–17624

    Abstract: Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, ... ...

    Abstract Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter
    Language English
    Publishing date 2020-08-28
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.103788
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.89: Show issues Location:
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  6. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3344: Show issues Location:
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  7. Article ; Online: CD44 impacts glomerular parietal epithelial cell changes in the aged mouse kidney.

    Hamatani, Hiroko / Eng, Diana G / Hiromura, Keiju / Pippin, Jeffrey W / Shankland, Stuart J

    Physiological reports

    2020  Volume 8, Issue 12, Page(s) e14487

    Abstract: CD44 contributes to the activation of glomerular parietal epithelial cells (PECs). Although CD44 expression is higher in PECs of healthy aged mice, the biological role of CD44 in PECs in this context remains unclear. Accordingly, young (4 months) and ... ...

    Abstract CD44 contributes to the activation of glomerular parietal epithelial cells (PECs). Although CD44 expression is higher in PECs of healthy aged mice, the biological role of CD44 in PECs in this context remains unclear. Accordingly, young (4 months) and aged (24 months) CD44
    MeSH term(s) Age Factors ; Animals ; Disease Models, Animal ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Female ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/metabolism ; Kidney Diseases/genetics ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Male ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Podocytes/metabolism ; Podocytes/pathology ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances Cd44 protein, mouse ; Hyaluronan Receptors ; mTOR protein, mouse (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Mapk3 protein, mouse (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
    Language English
    Publishing date 2020-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2724325-4
    ISSN 2051-817X ; 2051-817X
    ISSN (online) 2051-817X
    ISSN 2051-817X
    DOI 10.14814/phy2.14487
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Can podocytes be regenerated in adults?

    Shankland, Stuart J / Freedman, Benjamin S / Pippin, Jeffrey W

    Current opinion in nephrology and hypertension

    2017  Volume 26, Issue 3, Page(s) 154–164

    Abstract: Purpose of review: Podocytes are critical components of the nephron filtration barrier and are depleted in many kidney injuries and disease states. Terminally differentiated adult podocytes are highly specialized, postmitotic cells, raising the question ...

    Abstract Purpose of review: Podocytes are critical components of the nephron filtration barrier and are depleted in many kidney injuries and disease states. Terminally differentiated adult podocytes are highly specialized, postmitotic cells, raising the question of whether the body has any ability to regenerate lost podocytes. This timely question has recently been illuminated by a series of innovative studies. Here, we review recent progress on this topic of significant interest and debate.
    Recent findings: The innovation of genetic labeling techniques enables fate tracing of individual podocytes, providing the strongest evidence yet that podocytes can be replaced by nearby progenitor cells. In particular, two progenitor pools have recently been identified in multiple studies: parietal epithelial cells and cells of renin lineage. These studies furthermore suggest that podocyte regeneration can be enhanced using ex-vivo or pharmacological interventions.
    Summary: Recent studies indicate that the podocyte compartment is more dynamic than previously believed. Bidirectional exchange with neighboring cellular compartments provides a mechanism for podocyte replacement. Based on these findings, we propose a set of criteria for evaluating podocyte regeneration and suggest that restoration of podocyte number to a subsclerotic threshold be targeted as a potentially achievable clinical goal.
    Language English
    Publishing date 2017-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/MNH.0000000000000311
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    Zs.A 3686: Show issues Location:
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  9. Article ; Online: Podocyte injury at young age causes premature senescence and worsens glomerular aging.

    Veloso Pereira, Beatriz Maria / Zeng, Yuting / Maggiore, Joseph C / Schweickart, Robert Allen / Eng, Diana G / Kaverina, Natalya / McKinzie, Sierra R / Chang, Anthony / Loretz, Carol J / Thieme, Karina / Hukriede, Neil A / Pippin, Jeffrey W / Wessely, Oliver / Shankland, Stuart J

    American journal of physiology. Renal physiology

    2023  Volume 326, Issue 1, Page(s) F120–F134

    Abstract: As life expectancy continues to rise, age-related diseases are becoming more prevalent. For example, proteinuric glomerular diseases typified by podocyte injury have worse outcomes in the elderly compared with young patients. However, the reasons are not ...

    Abstract As life expectancy continues to rise, age-related diseases are becoming more prevalent. For example, proteinuric glomerular diseases typified by podocyte injury have worse outcomes in the elderly compared with young patients. However, the reasons are not well understood. We hypothesized that injury to nonaged podocytes induces senescence, which in turn augments their aging processes. In primary cultured human podocytes, injury induced by a cytopathic antipodocyte antibody, adriamycin, or puromycin aminonucleoside increased the senescence-related genes
    MeSH term(s) Middle Aged ; Humans ; Mice ; Animals ; Aged ; Podocytes/metabolism ; Glomerulosclerosis, Focal Segmental/metabolism ; Kidney Glomerulus/metabolism ; Kidney Diseases/metabolism ; Aging ; Doxorubicin/toxicity ; Doxorubicin/metabolism
    Chemical Substances Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00261.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.89: Show issues Location:
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  10. Article ; Online: Differential expression of parietal epithelial cell and podocyte extracellular matrix proteins in focal segmental glomerulosclerosis and diabetic nephropathy.

    Chan, Gek Cher / Eng, Diana G / Miner, Jeffrey H / Alpers, Charles E / Hudkins, Kelly / Chang, Anthony / Pippin, Jeffrey W / Shankland, Stuart J

    American journal of physiology. Renal physiology

    2019  Volume 317, Issue 6, Page(s) F1680–F1694

    Abstract: In healthy glomeruli, parietal epithelial cell (PEC)-derived extracellular matrix (ECM) proteins include laminin- ... ...

    Abstract In healthy glomeruli, parietal epithelial cell (PEC)-derived extracellular matrix (ECM) proteins include laminin-β
    MeSH term(s) Agrin/metabolism ; Animals ; Collagen Type IV/metabolism ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology ; Epithelial Cells/metabolism ; Extracellular Matrix Proteins/metabolism ; Glomerulosclerosis, Focal Segmental/metabolism ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/metabolism ; Kidney/metabolism ; Kidney/pathology ; Laminin/metabolism ; Male ; Mice ; Mice, Knockout ; Mice, Obese ; Podocytes/metabolism
    Chemical Substances Agrin ; COL4A4 protein, human ; Collagen Type IV ; Extracellular Matrix Proteins ; Hyaluronan Receptors ; Laminin ; laminin beta2 (124148-86-3)
    Language English
    Publishing date 2019-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.00266.2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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