Uric acid mediates kidney tubular inflammation through the LDHA/ROS/NLRP3 pathway
| Autor: | Jun Ouyang, Hui Wang, Yumei Gan, Jiangnan Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Clinical and Experimental Hypertension, Vol 46, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 10641963 1525-6006 1064-1963 |
| DOI: | 10.1080/10641963.2024.2424834 |
| Popis: | Purpose Hyperuricemia (HUA) is an important factor leading to chronic kidney disease (CKD). The kidney tubular inflammatory response is activated in HUA. This study aimed to investigate whether lactate dehydrogenase A (LDHA) is involved in mediating uric acid-induced kidney tubular inflammatory response.Methods In vivo, an HUA mouse model was established by continuous intraperitoneal injection of potassium oxonate (PO) for one week. A total of 18 C57BL/6J male adult mice were divided into three groups: control group, HUA group, and HUA+oxamate group, with six mice in each group. Oxamate was intraperitoneally injected into the mice one hour after PO injection. In vitro, an HUA model was simulated by stimulating HK-2 cells with uric acid. Oxamate and tempol inhibited LDHA and reactive oxygen species (ROS) in HK-2 cells.Results In HUA mice, blood uric acid levels were significantly elevated. LDHA in kidney tubular cells was significantly increased in both in vivo and in vitro HUA models, accompanied by an increase in kidney tubular inflammation and ROS. Mechanistically, LDHA mediates uric acid-induced inflammation to kidney tubular cells through the ROS/NLRP3 pathway. Pharmacologic inhibition of LDHA or ROS in kidney tubular cells can significantly ameliorate inflammation response caused by uric acid.Conclusions LDHA in kidney tubular cells significantly was increased in HUA models. LDHA mediates kidney inflammation response induced by uric acid through the ROS/NLRP3 pathway. This study may provide a new intervention target for preventing kidney tubular inflammation caused by uric acid. |
| Databáze: | Directory of Open Access Journals |
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