Article
Genetics & Heredity
Magdalena Patrycja Woznowski, Sebastian Alexander Potthoff, Eva Koenigshausen, Raphael Haase, Henning Hoch, Catherine Meyer-Schwesinger, Thorsten Wiech, Johannes Stegbauer, Lars Christian Rump, Lorenz Sellin, Ivo Quack
Summary: Chronic hyperglycemia, such as in diabetes mellitus, can lead to early signs of glomerular damage with microalbuminuria. Even acute hyperglycemia can increase glomerular permeability before structural damage occurs. A deeper understanding of the molecular mechanisms of albuminuria is desired. P38 MAPK signaling is involved in the development of hyperglycemia-induced albuminuria. Acute hyperglycemia triggers endocytosis of nephrin, the key molecule of the slit diaphragm.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Biochemistry & Molecular Biology
Ki Ryang Na, Jin Young Jeong, Jin Ah Shin, Yoon-Kyung Chang, Kwang-Sun Suh, Kang Wook Lee, Dae Eun Choi
Summary: Recent studies have shown that mitochondrial disruption in podocytes can lead to glomerular diseases, particularly diabetic nephropathy. Deficiency of CRIF1 gene results in podocyte dysfunction and progressive glomerular sclerosis and tubulointerstitial diseases in mice. The study demonstrates a link between podocyte mitochondrial dysfunction and the development of glomerular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Makoto Tagaya, Shinji Kume, Mako Yasuda-Yamahara, Shogo Kuwagata, Kosuke Yamahara, Naoko Takeda, Yuki Tanaka, Masami Chin-Kanasaki, Yuki Nakae, Hideki Yokoi, Masashi Mukoyama, Naotada Ishihara, Masatoshi Nomura, Shin-ichi Araki, Hiroshi Maegawa
Summary: The mechanisms underlying the progression from endothelial damage to podocyte damage in diabetic kidney disease (DKD) and the development of massive proteinuria are investigated. Dynamin-related protein 1 (Drp1)-mediated regulation of mitochondrial fission in podocytes plays a role in the pathogenesis of proteinuria in DKD. Inhibition of mitochondrial fission in podocytes may represent a new therapeutic strategy for massive proteinuria in DKD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Transplantation
Anqun Chen, Jin Xu, Han Lai, Vivette D. D'Agati, Tian-Jun Guan, Shawn Badal, John Liles, John C. He, Kyung Lee
Summary: GS-444217 attenuated the development of collapsing focal glomerulosclerosis, podocyte loss, tubular injury, interstitial inflammation, and renal fibrosis in Tg26 mice. These improvements were accompanied by a marked reduction in albuminuria and improved renal function, suggesting that selective inhibition of ASK1 could be a potential adjunctive therapy for the treatment of HIVAN.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2021)
Review
Biochemistry & Molecular Biology
Wataru Fujii, Shigeru Shibata
Summary: This article reviews the extensive research conducted over the past 80 years on the regulation and action of the mineralocorticoid receptor (MR). It highlights the role of MR and the steroid hormone aldosterone in integrating responses of tubular cells and maintaining fluid homeostasis, as well as their dysregulation in kidney diseases. Experimental studies have shown the pathological consequences of MR overactivity and the mechanisms of enhanced MR signaling, while clinical studies have demonstrated the renoprotective effects of MR blockade. The article also discusses future areas of investigation, including the use of non-steroidal MR antagonists in non-diabetic kidney disease patients and the search for downstream mediators of renoprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Endocrinology & Metabolism
Julie Semenchuk, Katie Sullivan, Rahim Moineddin, Farid Mahmud, Allison Dart, Brandy Wicklow, Fengxia Xiao, Thalia Medeiros, James Scholey, Dylan Burger
Summary: The study found that interleukin-9 (IL-9) is associated with podocyte injury in early type 1 diabetes, and there are complex interactions between urinary IL-9, inflammatory cytokines, and ACR (urinary albumin/creatinine ratio, a measure of podocyte injury).
ACTA DIABETOLOGICA
(2022)
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
Medicine, Research & Experimental
Zongji Zheng, Shuting Zhang, Jiaqi Chen, Meina Zou, Yanlin Yang, Wen Lu, Shijing Ren, Xiangyu Wang, Wenhui Dong, Zikun Zhang, Ling Wang, Meiping Guan, Gladys L. Y. Cheing, Yaoming Xue, Yijie Jia
Summary: The feedback loop formed by HDAC2 and miR-205 plays a crucial role in regulating ECM production in tubular epithelial cells in individuals with DKD, suggesting its significance in the pathogenesis of DKD.
Article
Environmental Sciences
Xuefang Feng, Rong Zhou, Qian Jiang, Yanan Wang, Chen Yu
Summary: Chronic non-occupational exposure to cadmium is associated with renal injury in urban residents in China. Higher urinary cadmium levels are linked to an increased risk of low-grade albuminuria.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Medicine, General & Internal
John M. Basgen, Jenny S. Wong, Justina Ray, Susanne B. Nicholas, Kirk N. Campbell
Summary: The study showed that 2-week old WT and Cd2ap KO mice have similar levels of albuminuria, glomerular and mesangial volume, but Cd2ap KO mice have more extensive podocyte foot process effacement. This suggests that podocyte injury may be the initiating event leading to mesangial expansion and albuminuria in this model.
FRONTIERS IN MEDICINE
(2021)
Article
Cell Biology
Li Lin, Yuhong Ye, Haidong Fu, Weizhong Gu, Manli Zhao, Jingmiao Sun, Zhongkai Cao, Guoping Huang, Yi Xie, Fei Liu, Lu Li, Qiuyu Li, Jianhua Mao, Lidan Hu
Summary: This study reports a pathogenic mutation, ANLN E841K, in SRNS patients and investigates its effects on podocytes as well as the underlying mechanisms. The mutation was found to activate the PI3K/AKT/mTOR/apoptosis pathway, resulting in structural and functional changes in podocytes. The study highlights the important role of ANLN in maintaining the normal function of podocytes.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Medicine, General & Internal
Maggie Wang, Samson S. Peter, Chi D. Chu, Delphine S. Tuot, Jonathan H. Chen
Summary: The findings of this study suggest that nearly half of patients with CKD at high risk of progressing to kidney failure do not have a nephrologist visit within 1 year of established risk.
Article
Physiology
Luise A. Cullen-McEwen, James van der Wolde, Kotaro Haruhara, Leon Tribolet, John P. Dowling, Michael G. Bertram, Robert de Matteo, Fabian Haas, Jan Czogalla, Yusuke Okabayashi, James A. Armitage, M. Jane Black, Wendy E. Hoy, Victor G. Puelles, John F. Bertram
Summary: Low birth weight due to poor maternal nutrition is associated with low podocyte endowment. A mild podocyte deficit at birth does not necessarily result in glomerular pathology in adulthood, but postnatal podocyte loss combined with excessive body weight can lead to albuminuria and glomerulosclerosis. These findings offer new insights into the relationships between birth weight, podocyte indexes, postnatal weight, and glomerular pathology.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fengxia Zhang, Nan Jiang, Yan Gao, Zuyan Fan, Quhuan Li, Guibao Ke, Bohou Li, Qiong Wu, Ruiquan Xu, Shuangxin Liu
Summary: The study identified potential hub genes in diabetic nephropathy (DN) using differential gene expression analysis from glomeruli samples. PPBP was highlighted as a novel biomarker for DN podocyte injury. Various experiments were conducted to validate the efficiency of these selected genes as biomarkers, providing new insights for DN treatment and prevention.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Hayato Sasaki, Makoto Sugiyama, Nobuya Sasaki
Article
Biochemistry & Molecular Biology
Hayato Sasaki, Madoka Imanishi, Daisuke Fujikura, Makoto Sugiyama, Kyosuke Tanimoto, Yohei Mochiji, Yuki Takahashi, Koki Hiura, Masaki Watanabe, Takashige Kashimoto, Kenta Nakano, Tadashi Okamura, Nobuya Sasaki
Summary: The study successfully achieved specific depletion of all populations of mast cells in vivo using the Mcpt5/Cma1(DTR/+) mouse model, without causing a marked reduction in other cells. This new mouse model helps to further understand the functions of mast cells in the body and their impact on the immune system.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Masaki Watanabe, Yuki Takahashi, Koki Hiura, Kenta Nakano, Tadashi Okamura, Hayato Sasaki, Nobuya Sasaki
Summary: The study identified the R2140C variant of the Prkdc gene as the cause of susceptibility to ADR-induced nephropathy in mice. By generating B6 mice with this mutation, it was demonstrated that they exhibit susceptibility to ADR-induced nephropathy, similar to BALB/c, which can allow for the application of this model to genetically modified mice with a B6 background in future studies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Masaki Watanabe, Koya Shishido, Nao Kanehira, Koki Hiura, Kenta Nakano, Tadashi Okamura, Ryo Ando, Hayato Sasaki, Nobuya Sasaki
Summary: Most mitochondrial diseases are hereditary and highly heterogeneous. Cattle with the V79L mutation in the IARS1 protein exhibit weak calf syndrome, and recent studies have also found mutations in the IARS1 gene in pediatric mitochondrial diseases. This study generated hypomorphic IARS1(V79L) mutant mice to develop an animal model for IARS mutation-related disorders. The mutant mice showed mitochondrial hepatopathy and changes in mitochondrial function-associated protein levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Hayato Sasaki, Takeru Sasaki, Koki Hiura, Masaki Watanabe, Nobuya Sasaki
Summary: Cystinuria is a metabolic disorder caused by mutations in the SLC3A1 and SLC7A9 genes, resulting in excessive excretion of cystine and dibasic amino acids in the urine and increasing the risk of stone formation. This study presents a new mouse model of cystinuria, providing insights into the mechanisms of stone formation.