Review
Endocrinology & Metabolism
Jun-Qing Zhang, Ying-Ying Li, Xue-Yan Zhang, Zeng-Hui Tian, Cheng Liu, Shi-Tao Wang, Fa-Rong Zhang
Summary: Renal fibrosis is a common pathological manifestation of chronic kidney diseases and a major cause of end-stage renal disease, but its pathogenesis remains unclear. Renal tubular epithelial cell senescence has been found to accelerate the progression of renal fibrosis. Oxidative stress, telomere attrition, and DNA damage are the major causes of renal tubular epithelial cell senescence. Interventions and therapeutic strategies targeting cellular senescence, such as calorie restriction, exercise, Klotho, senolytics, and senostatics, show potential for the treatment of renal fibrosis.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Immunology
Sean E. DeWolf, Sashi G. Kasimsetty, Alana A. Hawkes, Lisa M. Stocks, Sunil M. Kurian, Dianne B. McKay
Summary: This study demonstrates for the first time that endogenous DAMPs released from injured RTECs directly activate PRR signaling in healthy RTECs. These findings provide new insights for the treatment of renal IRI.
Article
Biochemistry & Molecular Biology
Theodoros Eleftheriadis, Georgios Pissas, Spyridon Golfinopoulos, Maria Efthymiadi, Christina Poulianiti, Maria Anna Polyzou Konsta, Vassilios Liakopoulos, Ioannis Stefanidis
Summary: This study evaluated the response of renal proximal tubular epithelial cells (RPTECs) to high albumin concentration, focusing on the unfolded protein response (UPR) and DNA damage response (DDR). The results showed that albumin led to reactive oxygen species (ROS) overproduction and protein modification, which activated both UPR and DDR. This resulted in cellular apoptosis, senescence, and epithelial-to-mesenchymal transition (EMT). While agents against endoplasmic reticulum stress (ERS) only partially alleviated the harmful effects, inhibiting ROS upregulation prevented both UPR and DDR. Therefore, suppressing ROS overproduction may be more effective in mitigating the deleterious effects of albumin overload.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mohanraj Sadasivam, Chunfa Jie, Abdel Rahim A. Hamad
Summary: Research on the regulation of kidney T cell proliferation by renal tubular epithelial cells (RTECs) reveals that RTECs stimulate polyclonal proliferation of kidney T cells through cell-cell contact, independent of major histocompatibility complex, and regulated by CD155, αVβ3 integrin, and vitronectin. Peripheral CD4 and CD8 show resistance to this stimulation, while the minor subset of double-negative (DN) T cells are responsive. This study has conceptual implications for understanding the role of different cell types in regulating systemic and organ-specific T cell homeostasis.
Article
Cell Biology
Shu Yang, Guangyan Yang, Xinyu Wang, Jiaqing Xiang, Lin Kang, Zhen Liang
Summary: This study demonstrates the anti-fibrotic role of SIRT2 in renal tubules and hepatocytes. SIRT2 inhibits fibrotic gene expression by reducing the activation of the TGF-beta signaling pathway. It interacts with and deacetylates SMAD2 and SMAD3 to promote their degradation and decrease the activation of SMAD3.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Christiana Magkrioti, Georgia Antonopoulou, Dionysios Fanidis, Vaia Pliaka, Theodore Sakellaropoulos, Leonidas G. Alexopoulos, Christoph Ullmer, Vassilis Aidinis
Summary: This study investigated the response of human proximal tubular epithelial cells to LPA and other pathological stimuli, identifying signaling pathways and inflammatory factors that may play a role in the pathogenesis of CKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Peipei Wang, Jing Ouyang, Zhanjun Jia, Aihua Zhang, Yunwen Yang
Summary: The prevalence of renal diseases is increasing globally, yet the pathogenesis and effective treatments are still unclear. DNA damage and the related DNA damage response have been identified as common factors in acute kidney injury (AKI) and chronic kidney disease (CKD). Reactive oxygen species induced DNA damage is a common type involved in the development of these conditions. Recent developments in the field of DNA damage have provided insights into the role of DNA damage and DNA damage response in renal tubular epithelial cell injury. Focusing on DNA damage and DNA damage response may offer valuable diagnostic biomarkers and treatment strategies for renal diseases.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hang Guo, Ting Fang, Ying Cheng, Ting Li, Jing-Ru Qu, Chao-fei Xu, Xiao-qing Deng, Bei Sun, Li -Ming Chen
Summary: High fructose intake is a risk factor for kidney injury, and the specific mechanism is still unclear. ChREBP-beta, an active form of ChREBP, is involved in the regulation of fructose metabolism. Overexpression of ChREP-beta leads to ferroptosis and kidney injury in renal tubular epithelial cells. TXNIP, which is upregulated by ChREP-beta, is associated with ferroptosis. Metformin can inhibit the transcription of TXNIP by down-regulating ChREP-beta, thus alleviating high fructose-induced ferroptosis and kidney injury.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Hua Fu, Yong-Hong Gu, Juan Tan, Ye-Ning Yang, Guo-Hui Wang
Summary: The crosstalk between macrophages and tubular epithelial cells is important in the progression of renal fibrosis. In this study, the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of tubular epithelial cells, and the development of renal fibrosis was revealed. circACTR2 promoted the activation of NLRP3 inflammasome, inflammation in macrophages, and stimulated EMT and fibrosis of tubular epithelial cells by sponging miR-561. Knocking down circACTR2 and overexpressing miR-561 may benefit the treatment of renal fibrosis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Theodoros Eleftheriadis, Georgios Pissas, Georgios Filippidis, Maria Efthymiadi, Vassilios Liakopoulos, Ioannis Stefanidis
Summary: Gliflozins, such as dapagliflozin, can inhibit cell senescence pathways and prevent renal tubular epithelial cell (RPTEC) senescence. High glucose induces oxidative stress and leads to a senescence-associated secretory phenotype. Dapagliflozin reduces glucose consumption and inhibits related pathways, effectively preventing cell senescence. Investigating the effects of gliflozins on cell senescence has potential significance for the treatment of diabetic nephropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Bo Zhang, Xiang Chen, Feng Ru, Yu Gan, Bingsheng Li, Weiping Xia, Guoyu Dai, Yao He, Zhi Chen
Summary: The study demonstrates the role of ferroptosis in renal fibrosis induced by unilateral ureteral obstruction. Inhibiting ferroptosis can alleviate the morphological and pathological changes of renal fibrosis and suppress the expression of profibrotic factors. Liproxstatin-1 may potentially be used as a therapeutic approach for UUO-induced renal fibrosis by inhibiting ferroptosis in renal tubular epithelial cells.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yao Zhang, Jianjian Zhang, Dengyuan Feng, Hai Zhou, Zeping Gui, Ming Zheng, Zhou Hang, Zijie Wang, Zengjun Wang, Min Gu, Ruoyun Tan
Summary: This study revealed that ferroptosis of renal tubular epithelial cells (RTECs) may contribute to renal tubular injury in chronic renal allograft dysfunction (CAD). TNF-alpha induced ferroptosis by inhibiting GPX4 transcription through upregulating IRF1 in RTECs. Ferroptotic RTECs might secrete profibrotic factors to activate neighboring fibroblasts or induce EMT in adjacent RTECs.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Medicine, General & Internal
Yinghong Liu, Mingyue He, Hao Xiong, Fang Yuan
Summary: This study found that high glucose can increase the expression of inflammation-related proteins NLRP3 and GSDMD in kidney tissues of DKD patients, and induce pyroptosis in HK-2 cells. There is a correlation between glucose concentration and pyroptosis, which is significant for the treatment of DKD patients.
FRONTIERS IN MEDICINE
(2022)
Article
Cell Biology
Linbo Guan, Ping Fan, Xinghui Liu, Rui Liu, Yu Liu, Huai Bai
Summary: The study investigated the effect of physiological direct current EF on renal epithelial cell motility, showing that EF enhanced the rate of cell migration and facilitated wound healing by activating specific signaling pathways. The results suggest that EFs can augment the migration of renal epithelial cells and promote wound closure through activation of Erk1/2, p38 MAPK, and Akt signaling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ying Yang, Chensheng Li, Xia Gu, Junhui Zhen, Suwei Zhu, Tingting Lv, Qiang Wan, Yi Liu
Summary: The study demonstrated that ING2 plays a crucial role in modulating mitochondrial respiration of TECs by regulating mtDNA transcription and the abundance of respiratory chain components. ING2 also showed to be involved in the ubiquitination of mitochondrial transcription factor MRPL12, affecting TEC mitochondrial function. Additionally, ING2-mediated modulation on mtDNA transcription and mitochondrial respiration were found to be associated with TEC injuries induced by serum deprivation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Nutrition & Dietetics
Shih-I. Chen, Chin-Ling Chiang, Chia-Ter Chao, Chih-Kang Chiang, Jenq-Wen Huang
Summary: Gustatory dysfunction may serve as an important risk factor for frailty in patients with chronic kidney disease, as better taste function and subjective taste perception were associated with a lower probability of frailty independent of clinical features. Interventions aimed at improving gustatory function deficits may potentially reduce frailty severity in this population.
JOURNAL OF RENAL NUTRITION
(2021)
Article
Food Science & Technology
Shih- Chen, Chin-Ling Chiang, Chia-Ter Chao, Chih-Kang Chiang, Jenq-Wen Huang
Review
Cell Biology
You-Tien Tsai, Hsiang-Yuan Yeh, Chia-Ter Chao, Chih-Kang Chiang
Summary: Vascular calcification refers to the deposition of calcium apatite within the vascular wall, which leads to vascular stiffening and loss of compliance. Mitochondrial dysfunction may play a pathogenic role in the process of vascular calcification, with SOD2 potentially exerting beneficial effects by attenuating mitochondrial reactive oxygen species. Additionally, SOD2 has been found to affect various cellular processes that contribute to the development of vascular calcification, suggesting its potential as a druggable target for future therapeutic strategies.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Oncology
Po-Ming Chow, Yu-Wei Chang, Kuan-Lin Kuo, Wei-Chou Lin, Shing-Hwa Liu, Kuo-How Huang
Summary: The study found that the CDK7 inhibitor THZ1 can suppress cancer stemness in urothelial carcinoma, providing a potential therapeutic strategy for both chemosensitive and chemoresistant cancers.
Review
Biochemistry & Molecular Biology
Jia-Huang Chen, Chia-Hsien Wu, Chih-Kang Chiang
Summary: ER stress is a trigger for the development of many kidney diseases, and unfolded protein responses (UPRs) play a role in restoring protein homeostasis under this stress. Modulating UPRs and ER proteostasis may have therapeutic potential for kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Jia-Huang Chen, Chia-Ter Chao, Jenq-Wen Huang, Kuan-Yu Hung, Shing-Hwa Liu, Der-Cherng Tarng, Chih-Kang Chiang
Summary: The study reveals that the accumulation of IS is associated with renal fibrosis and upregulation of BiP and CHOP. Administration of indole, a precursor of IS, exacerbates renal fibrosis, SASP, and activation of ER stress, while AST-120 attenuates these effects.
Article
Biochemistry & Molecular Biology
Chong-Sun Khoi, Yu-Wen Lin, Jia-Huang Chen, Biing-Hui Liu, Tzu-Yu Lin, Kuan-Yu Hung, Chih-Kang Chiang
Summary: This study demonstrates that OTA induces nephrotoxicity through ER stress-related apoptosis in human renal cells, with a pathway mediated by ROS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Chong-Sun Khoi, Jia-Huang Chen, Tzu-Yu Lin, Chih-Kang Chiang, Kuan-Yu Hung
Summary: OTA is a mycotoxin widely found in various foods and feeds, causing harmful effects on humans and animals, with the kidneys being the main target. Recent research has focused on the intracellular molecular interactions and signaling pathways of OTA-induced nephrotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Chia-Ter Chao, You-Tien Tsai, Wen-Ting Lee, Hsiang-Yuan Yeh, Chih-Kang Chiang
Summary: This study used a deep learning-based strategy to screen and identify plant compounds that could potentially be used for treating vascular calcification (VC). By integrating information from multiple databases and using a graph neural network architecture for prediction and validation, we successfully identified several potentially effective compounds.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Food Science & Technology
Jia-Huang Chen, Chih-Kang Chiang
Summary: Uremic toxins are harmful metabolites that accumulate in the body of patients with declining renal function, particularly in chronic kidney disease (CKD) patients. Clearing uremic toxins has become a conventional treatment in the clinic, but the clearance of uremic toxins in the early stage of acute kidney injury (AKI) is rarely emphasized, despite increasing evidence showing its correlation with injury severity or mortality.
Article
Biochemistry & Molecular Biology
Chong-Sun Khoi, Cai-Qin Xiao, Kuan-Yu Hung, Tzu-Yu Lin, Chih-Kang Chiang
Summary: This study investigated the mechanism of vascular dysfunction induced by palmitic acid, and revealed the crucial roles of XBP1s and OSGIN1 in maintaining endothelial cell migration and regulating autophagy.
Article
Biotechnology & Applied Microbiology
Chen-Yu Lin, Te- Weng, Jui-Zhi Loh, Ding-Cheng Chan, Chih-Kang Chiang, Kuan-Yu Hung, Shing-Hwa Liu
Summary: Low-intensity pulsed ultrasound (LIPUS) is a therapeutic ultrasound that can aid in bone fracture repair and soft tissue healing. This study aimed to investigate the protective potential of LIPUS on CKD-associated muscle wasting. The results showed that LIPUS treatment effectively improved muscle strength, prevented muscle mass loss, and reduced muscle atrophy-related protein expression in CKD mice.
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
(2023)
Article
Urology & Nephrology
Ching- Cheng, Woan-Jean Lin, Hui-Ting Liu, Yi-Ting Chen, Chih-Kang Chiang, Kung-Yu Hung
Summary: The study aimed to improve the self-care ability of peritoneal dialysis patients using LINE Chatbot with artificial intelligence. The results showed that Chatbot could deliver remote information, increase patient satisfaction, and have a similar effect as face-to-face education in preventing infection and reducing peritonitis rate.
Article
Biochemistry & Molecular Biology
Li-Ting Tsai, Te- Weng, Ting-Yu Chang, Kuo-Cheng Lan, Chih-Kang Chiang, Shing-Hwa Liu
Summary: The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). Exposure to IS can induce ferroptosis, characterized by iron accumulation, impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys.
Article
Cell Biology
Jia-Huang Chen, Chia-Hsien Wu, Jia-Rong Jheng, Chia-Ter Chao, Jenq-Wen Huang, Kuan-Yu Hung, Shing-Hwa Liu, Chih-Kang Chiang
Summary: This study investigated the role of XBP1, a key regulator of the unfolded protein response (UPR), in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). The findings demonstrated that XBP1 expression was attenuated after AKI and inversely correlated with the severity of renal fibrosis. XBP1 deficiency in mice resulted in exacerbated renal fibrosis. Silencing XBP1 in human proximal tubular epithelial cells led to cell cycle arrest and increased TGF-beta 1 secretion. The study also identified TNF receptor associated protein 1 (Trap1) as a potential downstream target of XBP1, and showed that Trap1 overexpression alleviated the profibrotic effects of XBP1 deficiency.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
