Long-term low-dose microcystin-LR exposure induces renal injury in mice by activating PI3K/AKT signaling pathway.
10.12122/j.issn.1673-4254.2022.10.07
- Author:
Xiao Fang LIANG
1
;
Yue YANG
2
;
Shuai Shuai XU
3
;
Ying LIU
1
;
Han Yu CHU
1
;
Yan TANG
1
;
Fei YANG
1
Author Information
1. School of Public Health, University of South China, Hunan Provincial Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China.
2. School of Public Health, Central South University, Changsha 410000, China.
3. Wuzhong District Center for Disease Control and Prevention, Suzhou 215100, China.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
PI3K/AKT signaling pathway;
inflammation;
kidney damage;
microcystin-LR
- MeSH:
Animals;
Male;
Mice;
HEK293 Cells;
Interleukin-10;
Interleukin-6/pharmacology*;
Kidney/metabolism*;
Mice, Inbred C57BL;
Phosphatidylinositol 3-Kinases/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
RNA, Messenger;
Signal Transduction;
Tumor Necrosis Factor-alpha/pharmacology*
- From:
Journal of Southern Medical University
2022;42(10):1486-1494
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the toxic effect of long-term low-dose exposure to microcystin-LR (MC-LR) on kidney and its underlying molecular mechanism.
METHODS:Forty male C57BL/6 mice were randomized into 4 groups for exposure to 0, 1, 60, and 120 μg/L MC-LR (mixed in drinking water) for 12 months, and the body and kidney weight changes and renal pathologies of the mice were observed. The renal function indexes, the mRNA expression levels of IL-6, TNF-α and IL-10, and relative expression levels of PI3K/AKT pathway proteins in the kidney of the mice were detected. These parameters were also detected in HEK293 cells treated with MC- LR, LY294002, or both.
RESULTS:The overall trend of body weight changes was consistent among the 4 groups of mice, and their kidney mass and kidney index underwent no significant changes. In mice exposed to 60 and 120 μg/L MC-LR, obvious renal structural damage and significant elevation of the BUN and SCr levels were observed (P < 0.05) with up-regulated levels of IL-6 and TNF-α mRNA and increased protein expressions of p-PI3K/PI3K and p-AKT/AKT in the renal tissues (P < 0.05). IL-10 mRNA expression was significantly decreased in all the exposure groups (P < 0.05). The levels of BUN and Cr increased significantly in MC-LR-treated HEK293 cells and decreased in cells treated with both MC-LR and LY294002 (P < 0.05). The mRNA expression levels of IL-6 and TNF-α increased and the level of IL-10 mRNA decreased obviously in MC-LR-treated cells, and the opposite changes were observed in the cells with the combined treatment (P < 0.05). The proteins levels of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated in MC-LR group and down-regulated in the combined treatment group (P < 0.05).
CONCLUSION:MC- LR can activate inflammatory response and induce renal structural and functional damages in mice by activating the PI3K/AKT signaling pathway.
