Article
Urology & Nephrology
Fang Li, Yili Fang, Qiyuan Zhuang, Meichu Cheng, Desmond Moronge, Hao Jue, Oded Meyuhas, Xiaoqiang Ding, Zhigang Zhang, Jian-Kang Chen, Huijuan Wu
Summary: The phosphorylation of ribosomal protein S6 (rpS6) plays a crucial role in podocyte hypertrophy and loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS). Inhibiting rpS6 phosphorylation can effectively attenuate podocyte hypertrophy and depletion, thereby reducing the formation of FSGS lesions.
KIDNEY INTERNATIONAL
(2022)
Article
Cell Biology
Lixia Wang, Jie Wang, Zhimin Wang, Jianhua Zhou, Yu Zhang
Summary: The study found that urine exosomal miR-193a levels were significantly higher in patients with primary FSGS compared to those with MCN and IgAN, and were positively correlated with glomerulosclerosis index. Exosomes from cultured podocytes could transport miR-193a-5p to recipient cells potentially through a calcium-dependent release mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lilas Batool, Krithika Hariharan, Yao Xu, Mario Kassmann, Dmitry Tsvetkov, Bjoern-Oliver Gohlke, Sylvia Kaden, Manfred Gossen, Bernd Nuernberg, Andreas Kurtz, Maik Gollasch
Summary: Mutations in TRPC6 gene cause familial focal segmental glomerulosclerosis (FSGS) and are inherited dominantly. Majority of TRPC6 mutations result in missense changes affecting calcium influx; however, the underlying molecular mechanisms for cell injury and kidney pathology remain unclear. A novel TRPC6 mutation (V691Kfs*) was identified in a large kindred without FSGS despite truncated TRPC6 protein. Functional studies showed that V691Kfs* mutation leads to closure of ion-conducting pathway and fully inactivates the TRPC6 channel-specific calcium influx, suggesting a complete loss-of-function phenotype. This study emphasizes the importance of increased calcium influx through TRPC6 for podocyte cell death.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Urology & Nephrology
Conxita Jacobs-Cacha, Ander Vergara, Clara Garcia-Carro, Irene Agraz, Nestor Toapanta-Gaibor, Gema Ariceta, Francesc Moreso, Daniel Seron, Joan Lopez-Hellin, Maria Jose Soler
Summary: Primary or idiopathic FSGS is a kidney disease involving podocytes that leads to heavy proteinuria and may progress to end-stage renal disease. It has a poor prognosis, with 15% of patients being resistant to treatment and 30-50% experiencing disease recurrence after kidney transplantation. While confirming the diagnosis of primary FSGS can be complex, efforts to improve diagnostic approaches are ongoing to enhance understanding of the disease.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Pediatrics
Rachel K. Cason, Anna Williams, Megan Chryst-Stangl, Guanghong Wu, Kinsie Huggins, Kaye E. Brathwaite, Brandon M. Lane, Larry A. Greenbaum, Vivette D. D'Agati, Rasheed A. Gbadegesin
Summary: This article describes a sibling pair with NUP93 mutations and collapsing FSGS. Their findings suggest that mutations in NUP93 and other nucleoporin genes may be associated with familial cFSGS.
FRONTIERS IN PEDIATRICS
(2022)
Article
Medicine, Research & Experimental
Su-Wei Hu, Yuan-Hung Wang, Jhy-Shrian Huang, Yea-Mey Yang, Chia-Chang Wu, Chao-Wen Cheng
Summary: The study found that vardenafil treatment can alleviate proteinuria, renal dysfunction, and hypercholesterolemia induced by focal segmental glomerulosclerosis, and improve the histopathological damage of the kidneys.
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
Pediatrics
Qing Yang, Dan Tang, Chun Gan, Mi Bai, Xiaomei Song, Wei Jiang, Qiu Li, Yaxi Chen, Aihua Zhang, Mo Wang
Summary: Whole exome sequencing of a 9-year-old girl with steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis (SRNS-FSGS) identified two novel compound heterozygous mutations in the CRB2 gene. These CRB2 abnormalities were found to be the underlying cause of SRNS-FSGS, affecting the integrity of podocyte slit diaphragm (SD) structure by reducing the phosphorylation level of the protein S1PR1.
PEDIATRIC NEPHROLOGY
(2023)
Article
Medicine, Research & Experimental
Taihei Suzuki, Masayuki Iyoda, Nobuhiro Kanazawa, Shohei Tachibana, Hirokazu Honda
Summary: Inhibition of PCSK9 can improve kidney disease by reducing urinary albumin and ameliorating podocytopathy through regulating lipid uptake and inflammation signaling pathways. This study suggests that targeting PCSK9 may serve as a potential therapeutic strategy for kidney disease.
LABORATORY INVESTIGATION
(2023)
Article
Urology & Nephrology
Ting Jia, Tong Xu, Bart Smeets, Eva Miriam Buhl, Marcus Johannes Moeller, Juergen Floege, Barbara Mara Klinkhammer, Peter Boor
Summary: The study suggests that PDGF-B and its receptor PDGFR-beta play a crucial role in the development and progression of FSGS by affecting the activation, proliferation, and fibrotic characteristics of PECs. The molecular crosstalk between podocytes and PECs mediated by PDGF-B and PDGFR-beta drives glomerulosclerosis and the progression of FSGS. Treatment with PDGF-B neutralizing antibody can improve kidney function and reduce the occurrence of FSGS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xu He, Lingling Yang, Meiqiu Wang, Pei Zhang, Ren Wang, Daxi Ji, Chunlin Gao, Zhengkun Xia
Summary: This study found that reduced expression of GPX4 is associated with focal segmental glomerulosclerosis (FSGS) and targeting ferroptosis could be a promising therapeutic option for FSGS patients. Treatment with the ferroptosis inhibitor Fer1 reduced proteinuria, prevented glomerulosclerosis, and attenuated podocyte injury in an FSGS mouse model.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Natalia Chebotareva, Anatoliy Vinogradov, Alexander G. Brzhozovskiy, Daria N. Kashirina, Maria I. Indeykina, Anna E. Bugrova, Marina Lebedeva, Sergey Moiseev, Evgeny N. Nikolaev, Alexey S. Kononikhin
Summary: The aim of this study was to determine the proteomic profile of urine from patients with FSGS and MCD. The results showed significant differences in protein profiles between patients with FSGS group 2 and FSGS group 1/MCD. Several proteins were identified as potential biomarkers for these diseases, including apolipoprotein A-IV, hemopexin, and components of the complement system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Urology & Nephrology
Johanna Odenthal, Sebastian Dittrich, Vivian Ludwig, Tim Merz, Katrin Reitmeier, Bjoern Reusch, Martin Hoehne, Zuelfue C. Cosgun, Maximilian Hohenadel, Jovana Putnik, Heike Goebel, Markus M. Rinschen, Janine Altmueller, Sybille Koehler, Bernhard Schermer, Thomas Benzing, Bodo B. Beck, Paul T. Brinkkoetter, Sandra Habbig, Malte P. Bartram
Summary: This study reports a case of a 4-year-old boy with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS). Molecular genetic testing identified a novel mutation in alpha-actinin-4 that is associated with the disease. The study showed that the mutation led to decreased stability of alpha-actinin-4, protein mislocalization, and cytoskeleton rearrangements. Using a Drosophila model, the researchers demonstrated the pathogenicity of the mutation.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Maximilian M. Gass, Sarah Borkowsky, Marie-Luise Lotz, Rebecca Siwek, Rita Schroeter, Pavel Nedvetsky, Stefan Luschnig, Astrid Rohlmann, Markus Missler, Michael P. Krahn
Summary: Drosophila nephrocytes, similar to mammalian podocytes, exhibit characteristics of epithelial cells. Research has shown that phospholipid PI(4,5)P2 plays a crucial role in slit diaphragm formation, while PI(3,4,5)P3 has minimal impact on nephrocyte function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Suramath Isaranuwatchai, Ankanee Chanakul, Chupong Ittiwut, Rungnapa Ittiwut, Chalurmpon Srichomthong, Vorasuk Shotelersuk, Kanya Suphapeetiporn, Kearkiat Praditpornsilpa
Summary: The spectra of underlying genetic variants for FSGS vary among different populations. A study on biopsy-proven FSGS patients in Thailand identified disease-associated pathogenic/likely pathogenic variants in 11.3% of the cases. Genetic testing before treatment was found to be important to avoid unnecessary treatment.
SCIENTIFIC REPORTS
(2023)
