دورية أكاديمية

Cell Profiling of Acute Kidney Injury to Chronic Kidney Disease Reveals Novel Oxidative Stress Characteristics in the Failed Repair of Proximal Tubule Cells

التفاصيل البيبلوغرافية
العنوان: Cell Profiling of Acute Kidney Injury to Chronic Kidney Disease Reveals Novel Oxidative Stress Characteristics in the Failed Repair of Proximal Tubule Cells
المؤلفون: Zhixiang Yu, Ying Zhou, Yuzhan Zhang, Xiaoxuan Ning, Tian Li, Lei Wei, Yingxue Wang, Xiao Bai, Shiren Sun
المصدر: International Journal of Molecular Sciences, Vol 24, Iss 14, p 11617 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: acute kidney injury, chronic kidney disease, failed repair of PT cells, oxidative stress, intercellular communication, single-nucleus RNA sequencing, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Chronic kidney disease (CKD) is a major public health issue around the world. A significant number of CKD patients originates from acute kidney injury (AKI) patients, namely “AKI–CKD”. CKD is significantly related to the consequences of AKI. Damaged renal proximal tubular (PT) cell repair has been widely confirmed to indicate the renal prognosis of AKI. Oxidative stress is a key damage-associated factor and plays a significant role throughout the development of AKI and CKD. However, the relationships between AKI–CKD progression and oxidative stress are not totally clear and the underlying mechanisms in “AKI–CKD” remain indistinct. In this research, we constructed unilateral ischemia–reperfusion injury (UIRI)-model mice and performed single-nucleus RNA sequencing (snRNA-seq) of the kidney samples from UIRI and sham mice. We obtained our snRNA-seq data and validated the findings based on the joint analysis of public databases, as well as a series of fundamental experiments. Proximal tubular cells associated with failed repair express more complete senescence and oxidative stress characteristics compared to other subgroups. Furthermore, oxidative stress-related transcription factors, including Stat3 and Dnmt3a, are significantly more active under the circumstance of failed repair. What is more, we identified abnormally active intercellular communication between PT cells associated with failed repair and macrophages through the APP–CD74 pathway. More notably, we observed that the significantly increased expression of CD74 in hypoxia-treated TECs (tubular epithelial cells) was dependent on adjacently infiltrated macrophages, which was essential for the further deterioration of failed repair in PT cells. This research provides a novel understanding of the process of AKI to CKD progression, and the oxidative stress-related characteristics that we identified might represent a potentially novel therapeutic strategy against AKI.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
1661-6596
Relation: https://www.mdpi.com/1422-0067/24/14/11617; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms241411617
URL الوصول: https://doaj.org/article/00d3798c81f24bbd8ae5762030313827
رقم الأكسشن: edsdoj.00d3798c81f24bbd8ae5762030313827
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
16616596
DOI:10.3390/ijms241411617