Article
Biochemistry & Molecular Biology
Weiyan Lai, Dan Luo, Yin Li, Yuanqing Li, Qianqian Wang, Zhaoyong Hu, Zengchun Ye, Hui Peng
Summary: Moderate exercise is important in attenuating diabetic kidney disease, and it has been found that irisin secreted by skeletal muscles protects the kidney by inhibiting abnormal activation of the PI3K/AKT/mTOR signaling pathway, restoring autophagy in podocytes. This suggests that irisin may become a new drug for prevention and treatment of diabetic nephropathy.
Article
Biochemistry & Molecular Biology
QianYu Lu, LiJiao Yang, Jing-Jie Xiao, Qing Liu, LiHua Ni, Jun-Wei Hu, Hong Yu, XiaoYan Wu, Bai -Fang Zhang
Summary: Renal tubular damage is a key factor in the development of diabetic kidney disease (DKD), with ferroptosis as the main pathological process. Empagliflozin has been suggested as a potential treatment for renal injury, but its effects on diabetic-related ferroptosis and underlying mechanisms are not fully understood. This study evaluated the influence of empagliflozin on renal injury using mouse models and cell lines, and found that it can decrease ferroptosis in DKD mice and high-glucose stimulated cells. The protective effects of empagliflozin are partially mediated by AMP-activated protein kinase (AMPK) and the NRF2 activation pathway. These findings offer important insights for novel treatment approaches for DKD.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Medicine, General & Internal
Nassim Mahtal, Olivia Lenoir, Pierre-Louis Tharaux
Summary: Diabetes is a major cause of renal failure, with endothelial cells and podocytes playing a crucial role in the progression of diabetic kidney disease through their intricate interactions.
FRONTIERS IN MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Dandan Chen, Yaoyu Liu, Junqi Chen, Hua Lin, Huijuan Guo, Yifan Wu, Yuan Xu, Yuan Zhou, Wei Zhou, Ruirui Lu, Jiuyao Zhou, Junbiao Wu
Summary: This study reveals that high glucose inhibits autophagy by activating the JAK/STAT pathway in mice and podocytes, leading to inefficient removal of damaged proteins and organelles, ultimately exacerbating podocyte injury and the progression of DKD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Urology & Nephrology
Jie Feng, Li Bao, Xuan Wang, Huilin Li, Yuqiang Chen, Wenzhen Xiao, Zhengzhe Li, Liyi Xie, Wanhong Lu, Hongli Jiang, Kyung Lee, John Cijiang He
Summary: With the widespread use of combination antiretroviral therapy, the prevalence of HIV-associated nephropathy has significantly decreased. However, chronic kidney disease (CKD) remains high among patients living with HIV, particularly when also affected by diabetes. The synergistic effects of HIV infection and diabetes in driving CKD progression highlight the importance of exploring potential therapeutic interventions.
KIDNEY INTERNATIONAL
(2021)
Article
Plant Sciences
Zhen Zhu, Guangxin Luan, Shiqiao Peng, Yunyun Fang, Qiongqiong Fang, Shuang Shen, Kaiyue Wu, Shengnan Qian, Weiping Jia, Jianping Ye, Li Wei
Summary: This study aims to clarify the therapeutic effect of Huangkui capsule (HKC) on renal tubular mitophagy in diabetic kidney disease (DKD). The results showed that HKC can ameliorate renal tubulopathy in DKD and induce mitophagy through up-regulation of the STING1/PINK1 pathway. These findings provide an innovative therapeutic basis for the treatment of DKD.
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
Biochemistry & Molecular Biology
Jun Feng, Zhaowei Chen, Yiqiong Ma, Xueyan Yang, Zijing Zhu, Zongwei Zhang, Jijia Hu, Wei Liang, Guohua Ding
Summary: This study reveals that AKAP1 phosphorylates Larp1 via PKC signaling activation to decrease mtDNA replication, which accelerates mitochondrial dysfunction and podocyte injury in DKD.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Xue-qi Liu, Ling Jiang, Yuan-yuan Li, Yue-bo Huang, Xue-ru Hu, Wei Zhu, Xian Wang, Yong-gui Wu, Xiao-ming Meng, Xiang-ming Qi
Summary: Wogonin has been shown to alleviate glomerulopathy and podocyte injury in diabetic kidney disease (DKD) by regulating the Bcl-2-mediated crosstalk between autophagy and apoptosis. The study also demonstrated the inhibitory effects of wogonin on cellular damage and apoptosis induced by high glucose, as well as its promotion of autophagy in podocytes.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Medicine, General & Internal
Kirsten E. Peters, Scott D. Bringans, Ronan S. O'Neill, Tasha S. C. Lumbantobing, James K. C. Lui, Timothy M. E. Davis, Michael K. Hansen, Richard J. Lipscombe
Summary: PromarkerD is a blood test that predicts kidney function decline in people with type 2 diabetes who may be missed by standard tests. This study found that canagliflozin was effective in reducing PromarkerD scores in T2D patients, especially those at high risk.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Can Yang, Zhen Zhang, Jieting Liu, Peijian Chen, Jialing Li, Haiying Shu, Yanhui Chu, Luxin Li
Summary: This paper discusses the pathologic research and drug therapy of diabetic kidney disease (DKD), focusing on the death processes and mechanisms of glomerular podocytes in DKD. The complexity and potential crosstalk between various modes of cell death are also examined, providing insights into podocyte death and laying the foundation for future targeted therapy strategies for DKD treatment.
MOLECULAR MEDICINE
(2023)
Article
Oncology
Mei Tao, Danna Zheng, Xudong Liang, Diandian Wu, Kang Hu, Juan Jin, Qiang He
Summary: The study demonstrates that TG may alleviate the effects of EMT and apoptosis in DKD by upregulating autophagy through the mTOR/Twist1 signaling pathway.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Pharmacology & Pharmacy
Xin Wei, Yabin Ma, Ya Li, Wenzhao Zhang, Yuting Zhong, Yue Yu, Li-Chao Zhang, Zhibin Wang, Ye Tu
Summary: Telmisartan can protect against early diabetic kidney injury by improving podocyte damage and mesangial cell proliferation. Interestingly, telmisartan has opposite effects on cell viability and apoptosis of podocytes and mesangial cells in a high-glucose environment. The anti-apoptotic effect of telmisartan on podocytes may be related to its inhibition of swiprosin-1 expression, while telmisartan induces high expression of PPARγ in mesangial cells and inhibits PKCβ1/TGFβ1 expression.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Oleg Palygin, Christine A. Klemens, Elena Isaeva, Vladislav Levchenko, Denisha R. Spires, Lashodya Dissanayake, Oksana Nikolaienko, Daria Ilatovskaya, Alexander Staruschenko
Summary: The study found that renal purinergic signaling undergoes significant remodeling in diabetes, leading to an increase in ATP-mediated intracellular calcium flux in podocytes. P2X4 and P2X7 were identified as the major receptors contributing to the augmented ATP-mediated intracellular calcium signaling in diabetic podocytes.
Article
Immunology
Sophie Carina Kunte, Julian A. Marschner, Martin Klaus, Tamisa Honda, Chenyu Li, Manga Motrapu, Christoph Walz, Maria Lucia Angelotti, Giulia Antonelli, Maria Elena Melica, Letizia De Chiara, Roberto Semeraro, Peter J. Nelson, Hans-Joachim Anders
Summary: This study demonstrated through single-cell transcriptome analysis and experiments that NLRP3 inflammasome expression in renal parenchymal cells is low or even nonexistent, and podocytes do not produce IL-1β and IL-18. Therefore, NLRP3-mediated glomerular inflammation is limited to immune cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Jinshan Wu, Zeguo Sun, Shumin Yang, Jia Fu, Ying Fan, Niansong Wang, Jinbo Hu, Linqiang Ma, Chuan Peng, Zhihong Wang, Kyung Lee, John Cijiang He, Qifu Li
Summary: This study utilizes single-cell RNA sequencing to reveal the specific responses of kidney cells to ARBs and SGLT2i, and identifies a novel PT subcluster that plays a significant role in DKD.
Review
Urology & Nephrology
Anqun Chen, Lijun Yin, Kyung Lee, John Cijiang He
Summary: Kidney disease is a major complication of viral infections, with both HIV-associated nephropathy (HIVAN) and COVID-19 patients showing similarities in renal issues and underlying mechanisms. The role of local infection and systemic effects in the pathogenesis of these diseases remains an area of ongoing research.
Article
Urology & Nephrology
Yifan Xie, E. Jing, Hong Cai, Fang Zhong, Wenzhen Xiao, Ronald E. Gordon, Lois Wang, Ya-Li Zheng, Aihua Zhang, Kyung Lee, John Cijiang He
Summary: Recent studies have shown that kidney tubular epithelial cell (TEC) injury plays an important role in the progression of diabetic kidney disease (DKD). In this study, researchers found that overexpression of the protein RTN1A worsened DKD in mice by enhancing tubular injury, tubulointerstitial fibrosis, and kidney function decline. However, RTN1A overexpression did not exacerbate diabetes-induced glomerular injury or albuminuria. The study also identified the involvement of RTN1A in regulating ER-mitochondrial contacts, which contributed to TEC injury and DKD progression.
KIDNEY INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Ka Lung Cheung, Anbalagan Jaganathan, Yuan Hu, Feihong Xu, Alannah Lejeune, Rajal Sharma, Cristina I. Caescu, Jamel Meslamani, Adam Vincek, Fan Zhang, Kyung Lee, Nilesh Zaware, Amina Abdul Qayum, Chunyan Ren, Mark H. Kaplan, John Cijiang He, Huabao Xiong, Ming-Ming Zhou
Summary: This study uncovers a previously unrecognized mechanism of self-directed cell type-specific regulation of the master transcription factor Stat3 through its own transcriptional target Hipk2 in Th17 cell differentiation. These findings provide insights into the regulation of Th17 cell immune functions and suggest a therapeutic strategy for developing targeted therapies for Th17-associated inflammatory disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Lin Ye, Yu Liu, Xuejing Zhu, Tongyue Duan, Chang Wang, Xiao Fu, Panai Song, Shuguang Yuan, Hong Liu, Lin Sun, Fuyou Liu, Kyung Lee, John Cijiang He, Anqun Chen
Summary: The study used digital spatial profiling to simultaneously analyze the mRNA and protein profiles in glomerular and periglomerular areas of ANCA-GN patients and MCD controls. The findings revealed that the severe rupture of Bowman's capsule in ANCA-GN patients led to the upregulation of secreted phosphoprotein-1 and its receptor CD44, which correlated positively with fibrotic markers. Additionally, both alternative and classic complement pathways were activated in ANCA-GN patients, and M1 macrophages were predominantly involved in the early stage of BC rupture while M2 macrophages were involved in the late stage and may contribute to crescent fibrosis. The loss of glomerular cells in ANCA-GN was likely mediated by apoptosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Qingqing Zhu, Shumin Yang, Chengguo Wei, Geming Lu, Kyung Lee, John Cijiang He, Ruijie Liu, Yifei Zhong
Summary: This study confirms the beneficial effects of puerarin in diabetic kidney disease (DKD) and uncovers its underlying mechanism. Puerarin protects the kidneys by inhibiting Gnai1 and activating the cAMP/PKA/CREB pathway in podocytes.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Urology & Nephrology
Jia Fu, Zeguo Sun, Xuan Wang, Tuo Zhang, Weijie Yuan, Fadi Salem, Samuel Mon-Wei Yu, Weijia Zhang, Kyung Lee, John Cijiang He
Summary: This article provides a comprehensive analysis of macrophage transcriptomic profiles in early DKD, highlighting the dynamic macrophage phenotypes in disease progression.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Yuqiang Chen, Ya Chen, Jia Fu, Zeguo Sun, Huilin Li, Wenzhen Xiao, E. Jing, Benjamin Y. Lo, Niansong Wang, Weijia Zhang, Mary E. Klotman, Paul E. Klotman, Jeffrey B. Kopp, Vivette D. D'Agati, John Cijiang He, Kyung Lee
Summary: HIV infection can lead to tubular epithelial cell injury, and the expression of HIV Vpr protein can induce tubulointerstitial damage and fibrosis similar to human HIV-associated nephropathy. Using a novel inducible tubular epithelial cell-specific Vpr transgenic mouse model, the study found that Vpr expression resulted in tubulointerstitial damage, inflammation, fibrosis, and tubular cyst development. This study is important for understanding the mechanisms of kidney disease progression and fibrosis.
KIDNEY INTERNATIONAL
(2023)
Editorial Material
Urology & Nephrology
Anqun Chen, Kyung Lee, John Cijiang He
Summary: Disulfiram, an inhibitor of FROUNT, attenuates crescentic GN by inhibiting the FROUNT-CCR2 interaction and macrophage migration and activation.
KIDNEY INTERNATIONAL
(2022)
Article
Biotechnology & Applied Microbiology
Hong Cai, Ya Chen, Ye Feng, Morad Asadi, Lewis Kaufman, Kyung Lee, Thomas Kehrer, Lisa Miorin, Adolfo Garcia-Sastre, Luca Gusella, Leyi Gu, Zhaohui Ni, Shan Mou, John Cijiang He, Weibin Zhou
Summary: Acute kidney injury is common in COVID-19 patients infected with SARS-CoV-2, but the direct impact of the virus on renal tubular cells is not well understood. This study found that SARS-CoV-2 activates STAT3 signaling and causes cellular injury in human renal tubular cells. The viral protein ORF3A augments NF-KB and STAT3 signaling, leading to increased expression of kidney injury molecule 1. In animal models and kidney autopsies of COVID-19 patients, elevated levels of TRIM59, an E3 ubiquitin ligase that interacts with ORF3A and STAT3, were observed, suggesting its significant role in renal tubular cell injury caused by SARS-CoV-2 infection.
Article
Chemistry, Multidisciplinary
Bhaskar C. C. Das, Pratik Yadav, Sasmita Das, Mariko Saito, Todd Evans
Summary: Here, we present the design and synthesis of boron-based bexarotene analogues as potential RXR agonists. A common intermediate was used to access different classes of analogues, which were then borylated to create novel borotenoids. This strategy enables the synthesis of new therapeutic agents and probes for studying retinoic acid signaling pathways.
Article
Medicine, Research & Experimental
Fang Zhong, Hong Cai, Jia Fu, Zeguo Sun, Zhengzhe Li, David Bauman, Lois Wang, Bhaskar Das, Kyung Lee, John Cijiang He
Summary: Podocyte injury and loss play a crucial role in glomerular diseases. Protein S and TYRO3 have been shown to protect against podocyte loss and attenuate glomerular disease progression. A TYRO3 agonist, compound 10, has demonstrated renoprotective effects in mouse models of nephropathy and type 2 diabetes.
Article
Multidisciplinary Sciences
Man Chen, Madhav C. Menon, Wenlin Wang, Jia Fu, Zhengzi Yi, Zeguo Sun, Jessica Liu, Zhengzhe Li, Lingyun Mou, Khadija Banu, Sui-Wan Lee, Ying Dai, Nanditha Anandakrishnan, Evren U. Azeloglu, Kyung Lee, Weijia Zhang, Bhaskar Das, John Cijiang He, Chengguo Wei
Summary: The study reveals the association of HCK with kidney inflammation and fibrosis and uncovers a mechanism of HCK regulating autophagy in macrophages, which affects their polarization, proliferation, and migration. Furthermore, a more selective HCK inhibitor is developed. The findings shed light on the role of HCK in regulating macrophage activation and polarization through autophagy in chronic kidney disease, suggesting the potential of selective HCK inhibitors as a new therapy for renal fibrosis.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Bhaskar C. Das, Pratik Yadav, Sasmita Das, John Cijiang He
Summary: In this study, we demonstrated a simple and efficient Pd-catalyzed C-4 borylation of structurally complex chloroquinolines, which can be further converted into various compounds and applied for the synthesis of potential inhibitors. This research provides new insights into the functionalization of quinolines for biomedical research.
