Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney

• Published in: Chemosphere (Oxford) Vol. 215; pp. 710 - 715
• Main Authors: Shi, Qunxiang, Jin, Xi, Fan, Ruifeng, Xing, Mengyuan, Guo, Jinming, Zhang, Ziwei, Zhang, Junmin, Xu, Shiwen
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2019
• Subjects: Animals; Autophagy; Autophagy - drug effects; Autophagy - genetics; Cadmium; Cadmium - metabolism; Cadmium - toxicity; Chickens - metabolism; Drug Interactions; Endoplasmic Reticulum Stress - drug effects; ER stress; Heat-Shock Proteins - metabolism; JNK; Kidney - metabolism; Kidney - pathology; MAP Kinase Signaling System; MicroRNAs - metabolism; miR-30a-GRP78; Selenium - metabolism; Selenium - pharmacology; ER stress; Cadmium; Autophagy; miR-30a-GRP78; JNK
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2018.10.019

Cadmium-mediated microRNAs have become a heavily researched topic. Few studies mention the regulation of autophagy by cadmium through microRNAs, especially regarding poultry. The kidney is one of the organs most severely affected by cadmium, as it is involved in the accumulation of metal ions; causing such types of damage as apoptosis, necrosis and autophagy to the body. However, the relationship between miR-30a and GRP78 in the chicken kidney during ER stress and autophagy via JNK has not been thoroughly elucidated to date. In our research, we randomly assigned 128 Hy-Line Brown laying chickens to four groups with different diet treatments. The four groups consisted of the control group (0.2 mg Se kg-1), the Se group (2 mg kg-1 of Na2SeO3), the Se + Cd group (150 mg kg-1 of CdCl2 and 2 mg kg-1 of Na2SeO3) and the Cd group (150 mg kg-1 of CdCl2). On the 90th day, we detected the expression of miR-30a, GRP78, ER stress-related genes, IRE-1-JNK and autophagy-related genes. Compared with the control group, the mRNA levels of IRE-1-JNK, ER stress-related genes, autophagy-related genes and GRP78 were significantly increased (P < 0.05), while the expression of miR-30a was significantly decreased (p < 0.05) in the Cd group. However, those changes were clearly alleviated in the Se + Cd group (p < 0.05). In summary, we demonstrated that Cd triggered an miR-30a-GRP78 signaling axis disorder, increasing ER stress and activating the IRE-1-JNK pathway, thereby promoting autophagy in the chicken kidney. Moreover, Se could antagonize the negative impact of Cd. •The targeting relationship of miR-30a-GRP78 was found in chicken exposed to Cd.•Cd can cause ER stress via the JNK pathway, increasing autophagy.•Se can antagonize miR-30a-GRP78 axis perturbation induced by Cd.•Se can alleviate ER stress by JNK pathway and later reduce autophagy induced by Cd.