The involvement of miR-6615-5p/Smad7 axis and immune imbalance in ammonia-caused inflammatory injury via NF-κB pathway in broiler kidneys

• Published in: Poultry science Vol. 99; no. 11; pp. 5378 - 5388
• Main Authors: Han, Qi, Tong, Jianyu, Sun, Qi, Teng, Xiaojie, Zhang, Hongfu, Teng, Xiaohua
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2020; Elsevier
• Subjects: ammonia; Ammonia - toxicity; Animals; broiler kidney; Chickens - genetics; Chickens - immunology; immune imbalance; Immunology, Health and Disease; Inflammation - chemically induced; inflammatory injury; Kidney - drug effects; Kidney - immunology; Kidney - physiopathology; MicroRNAs - metabolism; miR-6615/Smad7 axis; NF-kappa B - genetics; Smad7 Protein - metabolism; ammonia; immune imbalance; inflammatory injury; miR-6615/Smad7 axis; broiler kidney
• ISSN: 0032-5791; 1525-3171
• DOI: 10.1016/j.psj.2020.08.005

Ammonia (NH3), a toxic gas, has deleterious effects on chicken health in intensive poultry houses. MicroRNA can mediate inflammation. The complex molecular mechanisms underlying NH3 inhalation–caused inflammation in animal kidneys are still unknown. To explore the mechanisms, a broiler model of NH3 exposure was established. Kidney samples were collected on day 14, 28, and 42, and meat yield was evaluated on day 42. We performed histopathological examination, detected miR-6615-5p and mothers against decapentaplegic homolog 7 (Smad7), and determined inflammatory factors and cytokines in kidneys. The results showed that excess NH3 reduced breast weight and thigh weight, which indicated that excess NH3 impaired meat yield of broilers. Besides, kidney tissues displayed histopathological changes after NH3 exposure. Meanwhile, the increases of inducible nitric oxide synthase (iNOS) activity and nitric oxide content were obtained. The mRNA and protein expression of inflammatory factors, including nuclear factor-κB (NF-κB), cyclooxygenase-2, prostaglandin E synthases, and iNOS increased, indicating that NF-κB pathway was activated. T-helper (Th) 1 and regulatory T (Treg) cytokines were downregulated, whereas Th2 and Th17 cytokines were upregulated, suggesting the occurrence of Th1/Th2 and Treg/Th17 imbalances. In addition, we found that Smad7 was a target gene of miR-6615-5p in chickens. After NH3 exposure, miR-6615-5p expression was elevated, and Smad7 mRNA and protein expression were reduced. In summary, our results suggest that NH3 exposure negatively affected meat yield; and miR-6615/Smad7 axis and immune imbalance participated in NH3-induced inflammatory injury via the NF-κB pathway in broiler kidneys. This study is helpful to understand the mechanism of NH3-induced kidney injury and is meaningful to poultry health and breed aquatics.