Florfenicol induced renal inflammatory response and apoptosis via cell adhesion molecules signaling pathway

Abstract

Early use of florfenicol (FFC) can adversely affect the health of broilers. Our previous studies showed that FFC caused kidney injury in broilers. However, the mechanism by which FFC causes nephrotoxicity remains unclear. In order to further explore the regulatory effect of FFC on specific signal pathway in the injured kidneys and the interaction between genes and proteins in this signal pathway, the transcriptome and proteome sequencing were performed on the chick kidneys in the control group and the FFC treatment group. Then, the sequencing data were analyzed, and the screened genes and proteins were verified by real-time quantitative PCR (qPCR) and parallel reaction monitoring (PRM), respectively. The results of sequencing showed that FFC exposure altered significantly the expression levels of 657 genes and 477 proteins in chick kidneys. Among them, 9 significantly differentially expressed genes (including CD28, ICOS, BLB1, BLB2, DMB2, CLDN8, CLDN18, CLDN19, and NEGR1) and 3 significantly differentially expressed proteins (including CD28, ICOS, and CLDN8) were involved in the cell adhesion molecules signaling pathway. Further analysis found that, the changes of the above genes and proteins were related to inflammation and apoptosis of the tissues and histiocytes in chick kidneys. Therefore, the structure and morphology of renal tissues, the expression levels of inflammatory and apoptotic factors, and the apoptotic rate of renal histocytes were detected. It was found that compared with the control group, there was obvious inflammatory cell infiltration in renal tissues of the FFC treatment group. At the same time, the levels of pro-inflammatory factors and pro-apoptotic factors raised significantly, and the apoptotic rate of renal histocytes increased significantly. The above results confirmed that FFC induced inflammatory reaction and apoptosis in chick kidneys by activating the cell adhesion molecules signaling pathway.

Keywords: apoptosis; cell adhesion molecules signaling pathway; chick kidney; florfenicol; inflammation.