Article
Urology & Nephrology
Lydia Djenoune, Ritu Tomar, Aude Dorison, Irene Ghobrial, Heiko Schenk, Jan Hegermann, Lynne Beverly-Staggs, Alejandro Hidalgo-Gonzalez, Melissa H. Little, Iain A. Drummond
Summary: The study reveals the presence of cell-autonomous calcium signaling in podocyte development, which is a conserved mechanism in different species. Calcium signaling is released from endoplasmic reticulum stores and plays a critical role in podocyte morphology and foot process formation.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Hiroyuki Yamada, Naritoshi Shirata, Shinichi Makino, Takafumi Miyake, Juan Alejandro Oliva Trejo, Kanae Yamamoto-Nonaka, Mitsuhiro Kikyo, Maulana A. Empitu, Ika N. Kadariswantiningsih, Maiko Kimura, Koichiro Ichimura, Hideki Yokoi, Masashi Mukoyama, Akitsu Hotta, Katsuhiko Nishimori, Motoko Yanagita, Katsuhiko Asanuma
Summary: Podocytes play a crucial role in regulating the localization of Nephrin and Neph1, with MAGI-2 being essential for maintaining the integrity of the glomerular filtration barrier. Downregulation of MAGI-2 leads to reduced expression of slit-diaphragm backbone proteins, while its overexpression preserves their localization at intercellular junctions. The PDZ domains of MAGI-2 play a significant role in interacting with slit diaphragm backbone proteins in podocytes, suggesting a mechanism by which these proteins are maintained in their proper locations.
KIDNEY INTERNATIONAL
(2021)
Article
Physiology
Jiafa Ren, Xiaohan Lu, Gentzon Hall, Jamie R. Privratsky, Matthew J. Robson, Randy D. Blakely, Steven D. Crowley
Summary: Activation of interleukin-1 receptor in podocytes limits kidney glomerular damage by stimulating Akt signaling cascades, providing a protective role in the pathogenesis of glomerular disease.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Cell Biology
Dominik Spitz, Maria Comas, Lea Gerstner, Severine Kayser, Martin Helmstaedter, Gerd Walz, Tobias Hermle
Summary: Both mTOR signaling and autophagy play important roles in regulating podocyte homeostasis, regeneration, and aging, as well as in glomerular diseases. This study used Drosophila nephrocytes as a podocyte model and found that inhibition of mTOR signaling led to increased spacing between slit diaphragms. Activation or inhibition of mTOR signaling both resulted in decreased nephrocyte function, indicating a delicate balance of signaling activity is required for proper function. Furthermore, mTOR positively regulated cell size, survival, and the subcortical actin network, while basal autophagy in nephrocytes was necessary for survival and limited the expression of nephrin, but did not directly affect slit diaphragm formation or endocytic activity. Excessive, mTOR-dependent autophagy was primarily responsible for slit diaphragm misspacing. Overall, this study established an invertebrate podocyte model for exploring the role of mTOR signaling and autophagy, and revealed a direct regulation of slit diaphragm architecture by the mTOR/autophagy pathway.
Article
Integrative & Complementary Medicine
Ling Yan, Xiaoxiao Xu, Yanbo Fan, Lifang Zhang, Xiaojing Niu, Aimin Hu
Summary: This study suggests that Tangshen Decoction may have potential therapeutic effects in preventing and treating diabetic nephropathy. It can lower blood glucose levels, improve renal function, reduce urine protein excretion, and enhance podocyte autophagy.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Ashish K. Singh, Lakshmi P. Kolligundla, Justus Francis, Anil K. Pasupulati
Summary: HIF1 plays a crucial role in cellular adaptation to low oxygen conditions, but elevated levels of HIF1 during chronic hypoxia can contribute to the development of glomerular diseases and proteinuria. Podocyte injury due to chronic hypoxia may impair glomerular function and lead to proteinuria.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Urology & Nephrology
Veniamin Ivanov, Yoshiyasu Fukusumi, Ying Zhang, Hidenori Yasuda, Meiko Kitazawa, Hiroshi Kawachi
Summary: Synbindin, identified as an important molecule in glomeruli, shows altered expression in various nephrotic models before traditional markers like nephrin. Its downregulation is associated with slit diaphragm dysfunction, affecting podocyte morphology and the expression of slit diaphragm-related proteins.
AMERICAN JOURNAL OF NEPHROLOGY
(2021)
Article
Physiology
Kazuyoshi Yamamoto, Masahiro Okabe, Keiko Tanaka, Takashi Yokoo, Ira Pastan, Toshikazu Araoka, Kenji Osafune, Tomohiro Udagawa, Masahiro Koizumi, Taiji Matsusaka
Summary: This study clarifies why morphologically definitive apoptosis is rarely observed in podocytes in vivo. When caspase-3 is activated in podocytes, these cells are immediately detached from the glomerulus and lost in the urine before DNA fragmentation occurs. Detachment is facilitated by glomerular filtration. This phenomenon explains why podocytes in vivo rarely show TUNEL staining and never apoptotic bodies.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Urology & Nephrology
Haijiao Zhang, Lin Lin, Jianping Liu, Lifeng Pan, Zhijie Lin, Mingjie Zhang, Jiong Zhang, Ying Cao, Jinwei Zhu, Rongguang Zhang
Summary: The slit diaphragm is a specialized adhesion junction that forms the final filtration barrier in the kidney. Key components at the slit diaphragm can spontaneously undergo phase separation, driving the formation of highly dense condensates and recruitment of adhesion molecules. Mutations in these components can lead to impaired formation of slit diaphragm condensates and enrichment of key proteins, ultimately impacting kidney function.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Michael Mysh, John S. Poulton
Summary: This study identified four novel regulators of nephrocyte SDs: Dig, Lgl, Scrib, and Par-1, which constitute the basolateral polarity module and its effector kinase. The data suggest that these proteins work with apical polarity proteins to regulate SDs by promoting normal endocytosis and trafficking of SD proteins. The findings significantly advance our understanding of SD regulation by connecting basolateral polarity proteins to these processes, considering the importance of apical polarity proteins and SD protein trafficking in podocytopathies.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Multidisciplinary Sciences
Hui Sun, Hui Li, Jie Yan, Xiangdong Wang, Mengyuan Xu, Mingxia Wang, Baozhen Fan, Jieying Liu, Ninghua Lin, Xin Wang, Li Li, Shengtian Zhao, Yongfeng Gong
Summary: Although mature podocytes lack tight junctions, the tight junction integral membrane protein claudin-5 (CLDN5) is predominantly expressed on the plasma membranes of podocytes under normal conditions. The deletion of CLDN5 exacerbates podocyte injury and proteinuria in a diabetic nephropathy mouse model by reducing ZO1 expression, inducing nuclear translocation of ZONAB, and downregulating the expression of WNT inhibitory factor-1 (WIF1).
NATURE COMMUNICATIONS
(2022)
Review
Physiology
Li Feng, Hua-Pan Shu, Lu-Lu Sun, Yu-Chi Tu, Qian-Qian Liao, Li-Jun Yao
Summary: SLIT ligand and its receptor ROBO were initially recognized for their role in axon guidance in central nervous system development. In recent years, the role of the SLIT-ROBO signaling pathway has expanded to cell migration, tumor development, angiogenesis, and bone metabolism. This article reviews the advances in the study of the SLIT-ROBO pathway in various renal pathophysiological and kidney disorders and proposes new directions for further research in this field.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Urology & Nephrology
Kevin Gilhaus, Claudia Cepok, David Kamm, Beate Surmann, Pavel I. Nedvetsky, Jana Emich, Alina Sundukova, Katharina Saatkamp, Harald Nuesse, Juergen Klingauf, Dirk O. Wennmann, Britta George, Michael P. Krahn, Hermann-Joseph Pavenstaedt, Beate A. Vollenbroeker
Summary: Research has shown that Ajuba proteins regulate the connection between the slit diaphragm protein complex and the actin cytoskeleton in nephrocytes, while maintaining the Hippo pathway in an inactive state. Activation of the Hippo pathway reduces the level of Djub, while reducing Djub levels activates the Hippo pathway and leads to morphological changes in the slit diaphragm and increased permeability.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Endocrinology & Metabolism
Bin Wang, Jing-Yi Qian, Tao-Tao Tang, Li-Lu Lin, Nan Yu, Hong-Lei Guo, Wei-Jie Ni, Ling-Li Lv, Yi Wen, Zuo-Lin Li, Min Wu, Jing-Yuan Cao, Bi-Cheng Liu
Summary: The study revealed that deficiency in the VDR/Atg3 axis leads to SD-TJ transition and foot process effacement in diabetic nephropathy by blocking the p62-mediated autophagy pathway.
Article
Biochemistry & Molecular Biology
Eun Young Kim, Stuart E. Dryer
Summary: The study elucidated the initial transduction steps used by soluble urokinase plasminogen activator receptor (suPAR) in mouse podocytes, highlighting the interaction between receptor for advanced glycation end-products (RAGE) and integrin subunits. Utilizing RAGE antagonists like FPS-ZM1 may provide a potential therapeutic strategy for various clinical conditions associated with elevated serum suPAR levels.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
