Review
Urology & Nephrology
George Vasquez-Rios, Marina De Cos, Kirk N. Campbell
Summary: Apolipoprotein L1 (APOL1) high-risk variants are associated with an increased risk for kidney disease. Recent studies have provided mechanistic insights into the development of APOL1-mediated kidney diseases (AMKD) and proposed therapeutic strategies to improve clinical outcomes.
KIDNEY INTERNATIONAL REPORTS
(2023)
Article
Urology & Nephrology
Wei Gong, Jiayu Song, Jing Liang, Haoyang Ma, Wenxiao Wu, Yue Zhang, Li Yang, Songming Huang, Zhanjun Jia, Aihua Zhang
Summary: Emerging evidence suggests that downregulated expression of Lon protease 1 in podocytes is negatively correlated with urinary protein levels and glomerular pathology, playing a crucial role in podocyte injury and the progression of podocytopathy. Podocyte-specific deletion of Lon protease 1 induces mitochondrial dysfunction and podocyte injury, highlighting the potential therapeutic approach of regulating Lon protease 1 in podocytes for podocytopathy.
KIDNEY INTERNATIONAL
(2021)
Article
Cell Biology
Claire Bryant, Amy Webb, Alexander S. Banks, Dawn Chandler, Rajgopal Govindarajan, Shipra Agrawal
Summary: Podocytes are specialized epithelial cells that play a crucial role in maintaining kidney function. They express specific variants of the PPAR gamma gene, which are different from those found in adipose tissue. Understanding these podocyte-specific PPAR gamma variants could lead to the development of targeted therapeutic treatments.
Article
Urology & Nephrology
Andrew J. B. Watts, Keith H. Keller, Gabriel Lerner, Ivy Rosales, A. Bernard Collins, Miroslav Sekulic, Sushrut S. Waikar, Anil Chandraker, Leonardo V. Riella, Mariam P. Alexander, Jonathan P. Troost, Junbo Chen, Damian Fermin, Jennifer L. Yee, Matthew G. Sampson, Laurence H. H. Beck Jr, Joel M. Henderson, Anna Greka, Helmut G. Rennke, Astrid Weins
Summary: In a subset of patients with minimal change disease, circulating nephrin autoantibodies were detected during active disease but significantly reduced or absent during treatment response. These autoantibodies were correlated with podocyte-associated punctate IgG in renal biopsies. A steroid-dependent patient with childhood minimal change disease developed end stage kidney disease, with high pretransplant circulating nephrin autoantibodies associated with massive post-transplant recurrence of proteinuria.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Urology & Nephrology
Maximilian Schindler, Florian Siegerist, Tim Lange, Stefan Simm, Sophia-Marie Bach, Marianne Klawitter, Jochen Gehrig, Sheraz Gul, Nicole Endlich
Summary: This study developed a novel in vivo high-content screening assay using an FSGS-like zebrafish model, and identified belinostat and related pan-histone deacetylase inhibitors as potential drugs for treating FSGS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Review
Medicine, General & Internal
Teruhiko Yoshida, Khun Zaw Latt, Jurgen Heymann, Jeffrey B. Kopp
Summary: African-Americans have a three-fold higher rate of chronic kidney disease compared to European-Americans, largely attributed to genetic variants in the APOL1 gene. Despite many mechanisms reported in cell culture models, few have been proven to be effective in transgenic models.
FRONTIERS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Qisheng Lin, Khadija Banu, Zhaohui Ni, Jeremy S. Leventhal, Madhav C. Menon
Summary: Autophagy is a protective mechanism that helps cells maintain homeostasis and provide nutrition, with podocytes showing high levels of autophagy. Understanding the role and regulation of autophagy in podocyte injury may provide insights into novel therapeutic targets for glomerular disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Urology & Nephrology
Linus Butt, David Unnersjoe-Jess, Martin Hoehne, Robert Hahnfeldt, Dervla Reilly, Markus M. Rinschen, Ingo Plagmann, Paul Diefenhardt, Sebastian Braehler, Paul T. Brinkkoetter, Hjalmar Brismar, Hans Blom, Bernhard Schermer, Thomas Benzing
Summary: This study demonstrated the pathogenic effect of podocin R231Q on its own, supporting the notion of podocin R229Q contributing to genetic predisposition in adult patients.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Urology & Nephrology
Alla Mitrofanova, Antonio Fontanella, Matthew Tolerico, Shamroop Mallela, Judith Molina David, Yiqin Zuo, Marcia Boulina, Jin-Ju Kim, Javier Santos, Mengyuan Ge, Alexis Sloan, Wadih Issa, Margaret Gurumani, Jeffrey Pressly, Marie Ito, Matthias Kretzler, Sean Eddy, Robert Nelson, Sandra Merscher, George Burke, Alessia Fornoni
Summary: This study reveals the crucial role of STING activation in the progression of DKD and Alport syndrome, suggesting that targeting STING may provide a therapeutic option for glomerular diseases.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Laura Valles-Saiz, Rocio Peinado-Cahuchola, Jesus Avila, Felix Hernandez
Summary: Tau, a cytoskeletal protein mainly expressed in neurons, plays important roles in multiple cellular processes. This study reveals that Tau4R is the main isoform of tau expressed in the kidney, particularly in podocytes. Knockout mice without tau display a more dynamic cytoskeleton in podocytes and exhibit glomerular damage and reduced urinary creatinine.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Henning Hagmann, Naghmeh Hassanzadeh Khayyat, Mahsa Matin, Cem Oezel, He Chen, Astrid Schauss, Christoph Schell, Thomas Benzing, Stuart Dryer, Paul T. Brinkkoetter
Summary: Reactive oxygen species (ROS) generated in diabetes and systemic inflammatory diseases modify cellular lipids, which in turn affect the biophysical properties of cellular membranes. This study investigates the impact of lipid peroxidation on TRPC6 activity and glomerular function.
Article
Urology & Nephrology
Janina Mueller-Deile, Nina Sopel, Alexandra Ohs, Victoria Rose, Marwin Groener, Christoph Wrede, Jan Hegermann, Christoph Daniel, Kerstin Amann, Gunther Zahner, Mario Schiffer
Summary: This study demonstrates that miR-192-5p and miR-378a-3p are upregulated in the glomeruli of iMGN patients, while NPNT is reduced. Using zebrafish and mouse models, it was shown that overexpression of miR-192-5p and knockdown of npnt induced edema, proteinuria, and podocyte damage. GEC downregulates podocyte NPNT via exosomes containing miR-192-5p.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Review
Medicine, General & Internal
Xuefei Tian, Patricia Bunda, Shuta Ishibe
Summary: Endocytosis is a mechanism that internalizes and recycles plasma membrane components and transmembrane receptors via vesicle formation. Podocytes, specialized epithelial cells in the kidney, play a critical role in maintaining the integrity of the glomerular filtration barrier. Dysfunction of podocyte endocytosis is associated with the development and progression of proteinuria in chronic kidney disease. Understanding the mechanism of podocyte endocytosis may provide insights into maintaining normal filtration function and potential therapeutic strategies for proteinuric glomerular diseases.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Olivier Delezay, Sophie Hodin, Zhiguo He, Edouard Ollier, Xavier Delavenne
Summary: Unfractionated heparin affects podocyte function by increasing permeability and altering cytoskeleton organization and cell attachment.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Cell Biology
Claire Bryant, Rachel Cianciolo, Rajgopal Govindarajan, Shipra Agrawal
Summary: Adriamycin-induced nephropathy is a common model for studying FSGS, but its application in C57BL/6 mice is limited. We systematically investigated the specifics of ADR-nephrosis in C57BL/6 N and J substrains. Our findings showed that N substrain exhibited more severe proteinuria and renal lesions compared to J substrain. This provides a reproducible mouse model for FSGS in a previously assumed ADR-resistant strain and highlights the differences between J and N substrains.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Urology & Nephrology
Jun Matsuda, Kana Asano-Matsuda, Thomas M. Kitzler, Tomoko Takano
Summary: Rho GTPases play a crucial role in regulating the actin cytoskeleton and are implicated in the pathogenesis of proteinuric glomerular diseases. These GTPases are primarily regulated by three families of proteins – GEFs, GAPs, and GDIs – with their upstream regulatory mechanisms largely unknown in podocytes. Further studies are needed to bridge the knowledge gap in the field.
KIDNEY INTERNATIONAL
(2021)
Review
Urology & Nephrology
Richard W. Naylor, Mychel R. P. T. Morais, Rachel Lennon
Summary: The glomerular basement membrane (GBM) is crucial for kidney filtration, with studies revealing insights into its composition, assembly, developmental transitions, and filtration role. Defects in GBM components are associated with hereditary and acquired diseases, with current treatments focused on reducing intraglomerular pressure and addressing underlying causes. Therapies targeting GBM maintenance and repair could lead to new treatments for GBM-associated diseases.
NATURE REVIEWS NEPHROLOGY
(2021)
Editorial Material
Urology & Nephrology
Rachel Lennon, Alessia Fornoni
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Endocrinology & Metabolism
Alexandra Pokhilko, Gaia Brezzo, Lahiru Handunnetthi, Raphael Heilig, Rachel Lennon, Colin Smith, Stuart M. Allan, Alessandra Granata, Sanjay Sinha, Tao Wang, Hugh S. Markus, Alexandra Naba, Roman Fischer, Tom Van Agtmael, Karen Horsburgh, M. Zameel Cader
Summary: This study successfully extracted cerebrovascular ECM from mouse and human brain tissues and identified over 1000 proteins in the ECM-enriched fraction. The identification of 147 core ECM proteins in the human brain vascular matrisome and the connection between brain ECM proteins and cerebrovascular diseases, provides unique mechanistic insight and potential drug targets for cerebrovascular diseases.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Biology
Mychel R. P. T. Morais, Pinyuan Tian, Craig Lawless, Syed Murtuza-Baker, Louise Hopkinson, Steven Woods, Aleksandr Mironov, David A. Long, Daniel P. Gale, Telma M. T. Zorn, Susan J. Kimber, Roy Zent, Rachel Lennon
Summary: By studying kidney organoids, we have revealed the complex and dynamic nature of basement membrane assembly, and identified its importance in human development and disease.
Article
Biochemistry & Molecular Biology
Rebecca Preston, Qing-Jun Meng, Rachel Lennon
Summary: The circadian clock network in mammals is responsible for regulating various physiological processes in the body. Kidney disease is associated with the circadian system and extracellular matrix. Recent evidence suggests that cell-matrix interactions and the biomechanical properties of the matrix play a crucial role in regulating peripheral circadian rhythms. Studying the kidney matrisome can provide insights into the interactions between the extracellular matrix and intracellular time-keeping mechanisms.
Article
Pediatrics
Richard W. Naylor, Elizabeth Watson, Samantha Williamson, Rebecca Preston, J. Bernard Davenport, Nicole Thornton, Martin Lowe, Maggie Williams, Rachel Lennon
Summary: A novel homozygous truncating variant in CD151 was identified in a young child with nail dystrophy and persistent urinary tract infections presenting with nephrotic-range proteinuria. The imaging of patient kidney tissue revealed thickening of GBM and podocyte effacement. Functional testing in zebrafish confirmed that depletion of cd151 caused proteinuria, indicating the association of CD151 variant with nephrotic-range proteinuria and microscopic hematuria.
PEDIATRIC NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Ranjay Jayadev, Mychel R. P. T. Morais, Jamie M. Ellingford, Sandhya Srinivasan, Richard W. Naylor, Craig Lawless, Anna S. Li, Jack F. Ingham, Eric Hastie, Qiuyi Chi, Maryline Fresquet, Nikki-Maria Koudis, Huw B. Thomas, Raymond T. O'Keefe, Emily Williams, Antony Adamson, Helen M. Stuart, Siddharth Banka, Damian Smedley, David R. Sherwood, Rachel Lennon
Summary: By utilizing bioinformatic and in vivo approaches, we have identified a network of proteins involved in basement membrane regulation and function. This study highlights the complexity of basement membranes and their impact on human health.
Article
Urology & Nephrology
Richard W. Naylor, Emmanuel Lemarie, Anthony Jackson-Crawford, J. Bernard Davenport, Aleksandr Mironov, Martin Lowe, Rachel Lennon
Summary: Zebrafish is a valuable model for studying kidney dysfunction. Researchers in this study created a transgenic zebrafish line that can quantitatively measure proteinuria, providing a new tool for screening drugs to alleviate proteinuria.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan
Summary: This study established a mouse model mimicking human idiopathic nephrotic syndrome (INS) by immunizing mice with Crb2 protein. The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. This model could be useful for studying the immunologic pathogenesis of human INS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Jun Matsuda, Dina Greenberg, Sajida Ibrahim, Mirela Maier, Lamine Aoudjit, Jennifer Chapelle, Cindy Baldwin, Yi He, Nathalie Lamarche-Vane, Tomoko Takano
Summary: CdGAP and beta-PIX are major regulatory proteins interacting with Rac1 in podocytes. CdGAP interacts with beta-PIX through its basic region and promotes their translocation in podocytes. Depletion of CdGAP leads to altered cell motility and increased Rac1 and Cdc42 activities in podocytes.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Alexander Eckersley, Mychel R. P. T. Morais, Matiss Ozols, Rachel Lennon
Summary: During ageing, there is a decline in the function of the glomerular and tubular basement membranes (BM) in the kidney, which is caused by damage accumulation to the extracellular matrix (ECM) protein structures. Peptide location fingerprinting (PLF) is used to identify ECM proteins with structure-associated differences in ageing. This study found alterations in functional regions of key BM components, reflecting age-dependent shifts in molecular and cellular interactions, oxidation, and the release of matrikines. The findings also revealed shared susceptibilities in BM components across species and organs.
Article
Multidisciplinary Sciences
Tho-Alfakar Al-Aubodah, Lamine Aoudjit, Giuseppe Pascale, Maneka A. Perinpanayagam, David Langlais, Martin Bitzan, Susan M. Samuel, Ciriaco A. Piccirillo, Tomoko Takano
Summary: Using single-cell RNA sequencing, the authors identify an extrafollicular B cell response in the blood samples of children with active INS, providing important insights into the B cell subsets in this disease.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Maryline Fresquet, Michael P. Lockhart-Cairns, Samuel J. Rhoden, Thomas A. Jowitt, David C. Briggs, Clair Baldock, Paul E. Brenchley, Rachel Lennon
Summary: Membranous nephropathy is an autoimmune kidney disease caused by autoantibodies targeting antigens present on glomerular podocytes. This study provides insights into the structure and key residues of the phospholipase A2 receptor (PLA2R) involved in autoantibody binding, and suggests potential drug targets for membranous nephropathy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Urology & Nephrology
Ainslie M. Hildebrand, Moumita Barua, Sean J. Barbour, Karthik K. Tennankore, Daniel C. Cattran, Tomoko Takano, Ping Lam, Sacha A. De Serres, Ratna Samanta, Michelle A. Hladunewich, Todd Fairhead, Penelope Poyah, D. Danielle Bush, Brian MacLaren, Dwight Sparkes, Philip Boll, Arenn Jauhal, Rohan John, Carmen Avila-Casado, Heather N. Reich
Summary: This study aims to establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in glomerulonephritis (GN) in Canada. The study involves recruiting adult patients from nine Canadian tertiary care centers and collecting long-term follow-up data and biospecimens to discover disease predictors and therapeutic targets for glomerulonephritis.
CANADIAN JOURNAL OF KIDNEY HEALTH AND DISEASE
(2022)
