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  1. Article ; Online: Targeting DNA Methylation in Podocytes to Overcome Chronic Kidney Disease.

    Hayashi, Kaori

    The Keio journal of medicine

    2023  Volume 72, Issue 3, Page(s) 67–76

    Abstract: The number of patients with chronic kidney disease (CKD) is on the rise worldwide, and there is urgent need for the development of effective plans against the increasing incidence of CKD. Podocytes, glomerular epithelial cells, are an integral part of ... ...

    Abstract The number of patients with chronic kidney disease (CKD) is on the rise worldwide, and there is urgent need for the development of effective plans against the increasing incidence of CKD. Podocytes, glomerular epithelial cells, are an integral part of the primary filtration unit of the kidney and form a slit membrane as a barrier to prevent proteinuria. The role of podocytes in the pathogenesis and progression of CKD is now recognized. Podocyte function depends on a specialized morphology with the arranged foot processes, which is directly related to their function. Epigenetic changes responsible for the regulation of gene expression related to podocyte morphology have been shown to be important in the pathogenesis of CKD. Although epigenetic mechanisms include DNA methylation, histone modifications, and RNA-based regulation, we have focused on DNA methylation changes because they are more stable than other epigenetic modifications. This review summarizes recent literature about the role of altered DNA methylation in the kidney, especially in glomerular podocytes, focusing on transcription factors and DNA damage responses that are closely associated with the formation of DNA methylation changes.
    MeSH term(s) Humans ; Podocytes/metabolism ; Podocytes/pathology ; DNA Methylation ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Renal Insufficiency, Chronic/genetics ; Kidney/metabolism ; Kidney/pathology
    Language English
    Publishing date 2023-06-03
    Publishing country Japan
    Document type Review ; Journal Article
    ZDB-ID 390981-5
    ISSN 1880-1293 ; 0022-9717
    ISSN (online) 1880-1293
    ISSN 0022-9717
    DOI 10.2302/kjm.2022-0017-IR
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Altered DNA methylation in kidney disease: useful markers and therapeutic targets.

    Hayashi, Kaori

    Clinical and experimental nephrology

    2022  Volume 26, Issue 4, Page(s) 309–315

    Abstract: Recent studies have demonstrated the association of altered epigenomes with lifestyle-related diseases. Epigenetic regulation promotes biological plasticity in response to environmental changes, and such plasticity may cause a 'memory effect', a ... ...

    Abstract Recent studies have demonstrated the association of altered epigenomes with lifestyle-related diseases. Epigenetic regulation promotes biological plasticity in response to environmental changes, and such plasticity may cause a 'memory effect', a sustained effect of transient treatment or an insult in the course of lifestyle-related diseases. We investigated the significance of epigenetic changes in several genes required for renal integrity, including the nephrin gene in podocytes, and the sustained anti-proteinuric effect, focusing on the transcription factor Krüppel-like factor 4 (KLF4). We further reported the role of the DNA repair factor lysine-acetyl transferase 5 (KAT5), which acts coordinately with KLF4, in podocyte injury caused by a hyperglycemic state through the acceleration of DNA damage and epigenetic alteration. In contrast, KAT5 in proximal tubular cells prevents acute kidney injury via glomerular filtration regulation by an epigenetic mechanism as well as promotion of DNA repair, indicating the cell type-specific action and roles of DNA repair factors. This review summarizes epigenetic alterations in kidney diseases, especially DNA methylation, and their utility as markers and potential therapeutic targets. Focusing on transcription factors or DNA damage repair factors associated with epigenetic changes may be meaningful due to their cell-specific expression or action. We believe that a better understanding of epigenetic alterations in the kidney will lead to the development of a novel strategy for chronic kidney disease (CKD) treatment.
    MeSH term(s) DNA Methylation ; DNA Repair ; Epigenesis, Genetic ; Humans ; Podocytes/metabolism ; Renal Insufficiency, Chronic/drug therapy
    Language English
    Publishing date 2022-01-13
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 1338768-6
    ISSN 1437-7799 ; 1342-1751
    ISSN (online) 1437-7799
    ISSN 1342-1751
    DOI 10.1007/s10157-022-02181-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Accumulating evidence suggests the potential of selective adrenal artery embolization as a standard treatment for primary aldosteronism.

    Nakamura, Toshifumi / Hayashi, Kaori

    Hypertension research : official journal of the Japanese Society of Hypertension

    2024  

    Language English
    Publishing date 2024-03-27
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/s41440-024-01656-0
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  4. Article ; Online: Predicting the laterality of the autonomous aldosterone production from adrenal vein sampling.

    Kinouchi, Kenichiro / Hayashi, Kaori

    Hypertension research : official journal of the Japanese Society of Hypertension

    2023  Volume 47, Issue 2, Page(s) 543–544

    MeSH term(s) Humans ; Aldosterone ; Vena Cava, Inferior/physiopathology ; Adrenal Glands/blood supply ; Hyperaldosteronism/diagnosis
    Chemical Substances Aldosterone (4964P6T9RB)
    Language English
    Publishing date 2023-11-02
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/s41440-023-01495-5
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  5. Article ; Online: In memoriam; a tribute to Takao Saruta, MD, PhD.

    Ichihara, Atsuhiro / Shibata, Hirotaka / Hayashi, Kaori / Saito, Ikuo

    Hypertension research : official journal of the Japanese Society of Hypertension

    2023  Volume 47, Issue 2, Page(s) 255–256

    MeSH term(s) Renin-Angiotensin System ; Renin/metabolism ; Aldosterone ; Angiotensin II
    Chemical Substances Renin (EC 3.4.23.15) ; Aldosterone (4964P6T9RB) ; Angiotensin II (11128-99-7)
    Language English
    Publishing date 2023-11-20
    Publishing country England
    Document type Editorial
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/s41440-023-01527-0
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  6. Article ; Online: Editorial (Thematic Issue: Epigenetic Modulations in Kidney Podocytes: A Possible Target of Treatment for Proteinuria).

    Hayashi, Kaori

    Current hypertension reviews

    2016  Volume 12, Issue 2, Page(s) 88

    MeSH term(s) Epigenesis, Genetic ; Humans ; Podocytes/physiology ; Proteinuria/therapy
    Language English
    Publishing date 2016-06-13
    Publishing country United Arab Emirates
    Document type Editorial
    ISSN 1875-6506
    ISSN (online) 1875-6506
    DOI 10.2174/157340211202160525001108
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Podocyte Ercc1 is indispensable for glomerular integrity.

    Hama, Eriko Yoshida / Nakamichi, Ran / Hishikawa, Akihito / Kihara, Miho / Abe, Takaya / Yoshimoto, Norifumi / Nishimura, Erina Sugita / Itoh, Hiroshi / Hayashi, Kaori

    Biochemical and biophysical research communications

    2024  Volume 704, Page(s) 149713

    Abstract: As life expectancy continues to increase, age-related kidney diseases are becoming more prevalent. Chronic kidney disease (CKD) is not only a consequence of aging but also a potential accelerator of aging process. Here we report the pivotal role of ... ...

    Abstract As life expectancy continues to increase, age-related kidney diseases are becoming more prevalent. Chronic kidney disease (CKD) is not only a consequence of aging but also a potential accelerator of aging process. Here we report the pivotal role of podocyte ERCC1, a DNA repair factor, in maintaining glomerular integrity and a potential effect on multiple organs. Podocyte-specific ERCC1-knockout mice developed severe proteinuria, glomerulosclerosis, and renal failure, accompanied by a significant increase in glomerular DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). ERCC1 gene transfer experiment in the knockout mice attenuated proteinuria and glomerulosclerosis with reduced DNA damage. Notably, CD44
    MeSH term(s) Humans ; Mice ; Animals ; Podocytes/metabolism ; Kidney Glomerulus/metabolism ; Kidney Diseases/metabolism ; Mice, Knockout ; Proteinuria/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Endonucleases/genetics ; Endonucleases/metabolism
    Chemical Substances Ercc1 protein, mouse (EC 3.1.-) ; DNA-Binding Proteins ; Endonucleases (EC 3.1.-)
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2024.149713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 116: Show issues Location:
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  8. Article: Epigenetic Alterations in Podocytes in Diabetic Nephropathy.

    Sugita, Erina / Hayashi, Kaori / Hishikawa, Akihito / Itoh, Hiroshi

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 759299

    Abstract: Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane-a barrier for proteinuria. ... ...

    Abstract Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane-a barrier for proteinuria. Podocytes are terminally differentiated cells without cell division or replenishment abilities. Therefore, podocyte damage is suggested to be one of the key factors determining renal prognosis. Recent studies, including ours, suggest that epigenetic changes in podocytes are associated with chronic kidney disease, including diabetic nephropathy. Furthermore, the association between DNA damage repair and epigenetic changes in diabetic podocytes has been demonstrated. Detection of podocyte DNA damage and epigenetic changes using human samples, such as kidney biopsy and urine-derived cells, may be a promising strategy for estimating kidney damage and renal prognoses in patients with diabetes. Targeting epigenetic podocyte changes and associated DNA damage may become a novel therapeutic strategy for preventing progression to end-stage renal disease (ESRD) and provide a possible prognostic marker in diabetic nephropathy. This review summarizes recent advances regarding epigenetic changes, especially DNA methylation, in podocytes in diabetic nephropathy and addresses detection of these alterations in human samples. Additionally, we focused on DNA damage, which is increased under high-glucose conditions and associated with the generation of epigenetic changes in podocytes. Furthermore, epigenetic memory in diabetes is discussed. Understanding the role of epigenetic changes in podocytes in diabetic nephropathy may be of great importance considering the increasing diabetic nephropathy patient population in an aging society.
    Language English
    Publishing date 2021-09-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.759299
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  9. Article ; Online: Effects of High Glucose and Lipotoxicity on Diabetic Podocytes.

    Nakamichi, Ran / Hayashi, Kaori / Itoh, Hiroshi

    Nutrients

    2021  Volume 13, Issue 1

    Abstract: Glomerular podocytes are highly differentiated cells that cover glomerular capillaries from the outside and have a characteristic morphology with numerous foot processes. The formation of slit membranes between the foot processes serves as a final ... ...

    Abstract Glomerular podocytes are highly differentiated cells that cover glomerular capillaries from the outside and have a characteristic morphology with numerous foot processes. The formation of slit membranes between the foot processes serves as a final filtration barrier for urine filtration from the blood. Podocyte damage causes disruption of the slit membrane, subsequent proteinuria and finally glomerulosclerosis, which is a common pathway in various types of chronic kidney disease (CKD). In recent years, there has been an increase in diabetes, due to rapid lifestyle changes, which is the main cause of CKD. Therefore, understanding the effect of diabetic status on podocytes is of great importance to establish a strategy for preventing CKD progression. In this review, we summarize altered glucose and lipid metabolism in diabetic podocytes and also discuss the reversibility of the changes in podocyte phenotype.
    MeSH term(s) Animals ; Apoptosis ; Blood Glucose ; Cell Survival ; Cholesterol/metabolism ; DNA Damage ; Diabetes Mellitus/blood ; Diabetes Mellitus/metabolism ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology ; Humans ; Hyperglycemia/blood ; Hyperglycemia/complications ; Ketone Bodies/metabolism ; Lipid Metabolism ; Podocytes/metabolism ; Podocytes/pathology ; Signal Transduction
    Chemical Substances Blood Glucose ; Ketone Bodies ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2021-01-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu13010241
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  10. Article ; Online: Amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin for predicting fetal inflammatory response syndrome based on histological chorioamnionitis and funisitis.

    Katsura, Daisuke / Tsuji, Shunichiro / Hayashi, Kaori / Tokoro, Shinsuke / Hoshiyama, Takako / Kita, Nobuyuki / Murakami, Takashi

    Taiwanese journal of obstetrics & gynecology

    2023  Volume 62, Issue 4, Page(s) 516–520

    Abstract: Objective: We aimed to analyze the predictive efficacy of amniotic fluid interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) for fetal inflammatory response syndrome (FIRS)-related infection.: Materials and methods: We included ...

    Abstract Objective: We aimed to analyze the predictive efficacy of amniotic fluid interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) for fetal inflammatory response syndrome (FIRS)-related infection.
    Materials and methods: We included singleton pregnancies classified into FIRS and non-FIRS groups. FIRS was defined as histologic chorioamnionitis and funisitis. Amniotic fluid samples were collected during vaginal delivery (VD) or cesarean section (CS). We compared amniotic fluid IL-6 and NGAL levels between the groups.
    Results: Forty-six pregnancies were analyzed and classified into 20 (43.5%) FIRS and 26 (56.5%) non-FIRS pregnancies. We observed significant differences in amniotic fluid IL-6 and NGAL. Amniotic fluid collection significantly influenced NGAL levels (p < 0.001). The area under the concentration-time curve (AUC), with optimal cutoff values, for amniotic fluid IL-6 and NGAL (VD and CS) levels was 0.948 (11,344 pg/mL), 0.800 (1180 ng/mL), and 0.946 (708 ng/mL), respectively.
    Conclusion: Amniotic fluid IL-6 and NGAL levels showed equivalent predictive ability for FIRS-related infection.
    MeSH term(s) Pregnancy ; Humans ; Female ; Chorioamnionitis/diagnosis ; Interleukin-6 ; Amniotic Fluid ; Lipocalin-2 ; Cesarean Section
    Chemical Substances Interleukin-6 ; Lipocalin-2
    Language English
    Publishing date 2023-06-12
    Publishing country China (Republic : 1949- )
    Document type Journal Article
    ZDB-ID 2202946-1
    ISSN 1875-6263 ; 1875-6263
    ISSN (online) 1875-6263
    ISSN 1875-6263
    DOI 10.1016/j.tjog.2023.03.014
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