Article
Pharmacology & Pharmacy
Binbin Cui, Xiying Hou, Mengjun Liu, Qing Li, Chao Yu, Shenglei Zhang, Yi Wang, Jun Wang, Shougang Zhuang, Feng Liu
Summary: This study reveals that SMYD2 plays a critical role in cisplatin-induced acute kidney injury. The specific inhibitor AZ505 suppresses SMYD2 expression, improving kidney function and reducing kidney damage. AZ505 exerts its protective effects through mechanisms including reducing cell injury and apoptosis, inhibiting inflammation, and promoting cell proliferation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Chen Guan, Chenyu Li, Xuefei Shen, Chengyu Yang, Zengying Liu, Ningxin Zhang, Lingyu Xu, Long Zhao, Bin Zhou, Xiaofei Man, Congjuan Luo, Hong Luan, Lin Che, Yanfei Wang, Yan Xu
Summary: Hexarelin was found to have a protective effect against I/R-induced AKI, improving renal function and inhibiting apoptosis by downregulating Caspase-3, Bax, Bad, and upregulating Bcl-2. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting its potential mechanism of anti-apoptosis effect.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Immunology
Maomao Sun, Jiaxin Li, Liangfeng Mao, Jie Wu, Zhiya Deng, Man He, Sheng An, Zhenhua Zeng, Qiaobing Huang, Zhongqing Chen
Summary: Recent studies have shown that upregulation of autophagy can attenuate sepsis-induced acute kidney injury (SAKI). The tumor suppressor protein p53 has been identified as a regulator of autophagy in various forms of acute kidney injury. Acetylation of p53 exacerbates AKI, but deacetylation can promote RTEC autophagy and alleviate SAKI.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Weimin Tang, Sudipta Panja, Chinmay M. Jogdeo, Siyuan Tang, Ling Ding, Ao Yu, Kirk W. Foster, Del L. Dsouza, Yashpal S. Chhonker, Heather Jensen-Smith, Hee-Seong Jang, Erika I. Boesen, Daryl J. Murry, Babu Padanilam, David Oupicky
Summary: This study demonstrates the synthesis of a novel siRNA carrier, C-CS, which shows potential for targeted delivery to injured kidneys. The C-CS/siRNA nanoparticles effectively accumulate and deliver therapeutic siRNAs to injured kidneys through CXCR4 binding, providing a new approach for AKI therapy.
Article
Biochemistry & Molecular Biology
Chi Zhang, Zhihuang Zheng, Kexin Xu, Guozhe Cheng, Huijuan Wu, Jun Liu
Summary: This study reveals that LATS2 deficiency exacerbates maladaptive repair after acute kidney injury and contributes to the progression of kidney disease. LATS2 deficiency activates p53 and increases the level of apoptotic molecules while decreasing the level of anti-apoptotic molecules. Inhibiting p53 effectively attenuates the damage caused by LATS2 deficiency. Additionally, overexpression of LATS2 decreases the expression of p53. In conclusion, LATS2 deficiency aggravates maladaptive repair through the regulation of the MDM2-p53 axis in acute kidney injury-induced damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Wei Huang, Weidang Xie, Hanhui Zhong, Shumin Cai, Qiaobing Huang, Youtan Liu, Zhenhua Zeng, Yanan Liu
Summary: This study discovered the dynamic changes of mitophagy in hepatocytes and demonstrated the protective effects of mitophagy activation on heat stroke-induced acute liver injury (HS-ALI). Inhibiting mitophagy worsened liver injury, while cytosolic p53 binding to Parkin inhibited mitophagy. Pharmacologic induction of mitophagy by inhibiting p53 may be a promising therapeutic approach for HS-ALI treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Weimin Tang, Yi Chen, Hee-Seong Jang, Yu Hang, Chinmay M. Jogdeo, Jing Li, Ling Ding, Chuhan Zhang, Ao Yu, Fei Yu, Kirk W. Foster, Babu J. Padanilam, David Oupicky
Summary: This study introduces a siRNA carrier designed for injured kidneys in AKI, showing potential to enhance therapeutic effects and improve kidney function. By inhibiting CXCR4 and p53 simultaneously, the PCX/sip53 polyplexes can selectively deliver therapeutic siRNA in AKI, reducing renal damage.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Zhe Hao, Qian Yuan, Hui Tang, Chuntao Lei, Yu Chen, Hua Su, Chun Zhang
Summary: P53 is a master regulator involved in the progression of acute kidney injury (AKI). The role of Mitotic arrest deficient 2 like 2 (MAD2B) in AKI is unclear. This study demonstrates that MAD2B functions as an endogenous suppressor of p53. MAD2B knockout enhances the upregulation of p53 in cisplatin-induced AKI, leading to renal function deterioration, G1 phase arrest, and apoptosis of tubular epithelial cells. Mechanistically, MAD2B deficiency activates anaphase-promoting complex/cyclosome (APC/C), which inhibits the p53-directed E3 ligase MDM2. Decreased MDM2 results in the upregulation of p53.
Article
Pharmacology & Pharmacy
Wenwen Wu, Ying Fu, Zhiwen Liu, Shaoqun Shu, Ying Wang, Chengyuan Tang, Juan Cai, Zheng Dong
Summary: Nicotinamide may protect against cisplatin-induced acute kidney injury by suppressing the PARP1/p53 pathway.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Heng Fan, Bin-jie Su, Jian-wei Le, Jian-hua Zhu
Summary: Pretreatment with SLDS can protect the kidneys of septic rats by inhibiting inflammation and apoptosis of kidney tubular epithelial cells.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Pharmacology & Pharmacy
Ruhao Yang, Haizhen Yang, Jie Wei, Wenqiang Li, Fang Yue, Yan Song, Xin He, Ke Hu
Summary: Using network pharmacology, this study predicted the active components and effective targets of LHQW in treating acute lung injury, and validated the protective mechanism of LHQW in ALI through experiments.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Medicine, General & Internal
Zhifen Wu, Junhui Deng, Hongwen Zhou, Wei Tan, Lirong Lin, Jurong Yang
Summary: Sepsis-associated acute kidney injury (SA-AKI) is commonly seen in ICU patients with severe sepsis and has a high mortality rate. Most patients develop AKI before drug treatment. Research has shown that the main mechanism of SA-AKI is vasodilation, hypotension, and shock leading to inadequate renal blood perfusion, resulting in ischemia and necrosis of renal tubular cells. Various forms of programmed cell death, including apoptosis, necroptosis, pyroptosis, and autophagy, play important roles in SA-AKI.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yong-Yu Yang, Ling Ye, Jing Chen, Yue Qiu, Ya-ling Yin, Peng Li
Summary: Cisplatin-induced acute kidney injury (AKI) is associated with high morbidity and mortality worldwide. Dok3, a member of the adaptor protein family, plays a critical role in regulating apoptosis and inflammation in cisplatin-induced AKI, suggesting it as a potential therapeutic target for AKI.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Ajinath Kale, Himanshu Sankrityayan, Anil Bhanudas Gaikwad
Summary: This study aimed to explore the mechanisms of Klotho regulation in hyperglycemia augmented AKI and evaluate epigenetic ways to restore Klotho expression in AKI-diabetes comorbidity. The findings suggest that hyperglycemia exacerbates AKI, but inhibition of kidney-specific HDACs can protect the kidney by restoring endogenous Klotho loss, preventing inflammation and apoptosis.
Article
Cell Biology
Da-Eun Kim, Hye Eun Byeon, Dae-Hoon Kim, Sang Geon Kim, Hyungshin Yim
Summary: Plk2 acts as an anti-oxidative and anti-inflammatory regulator by modulating the function of Nrf2 in kidney injury.
CELL BIOLOGY AND TOXICOLOGY
(2023)