Complement activation in a mouse model of cisplatin-induced renal interstitial fibrosis
10.3760/cma.j.cn441217-20210414-00120
- VernacularTitle:顺铂诱导的小鼠肾间质纤维化模型中存在补体活化
- Author:
Min FENG
1
;
Honghui ZENG
;
Weitang LIAO
;
Jianan SU
Author Information
1. 中山大学孙逸仙纪念医院肾内科，广州 510120
- Keywords:
Cisplatin;
Complement system proteins;
Computational biology;
Renal interstitial fibrosis;
RNA high-throughput sequencing
- From:
Chinese Journal of Nephrology
2021;37(10):809-816
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of cisplatin-induced renal interstitial fibrosis and provide a new idea for the prevention and treatment of renal interstitial fibrosis.Methods:Eight-week-old male C57BL/6 mice (specific pathogen-free) were used to carry out the experiment. The mice were divided into cisplatin group (10 mg/kg, n=6) and saline group ( n=6) with intraperitoneal injection on day 0, 7 and 21, and sacrificed on day 28. The kidney tissues were collected for RNA Illumina high-throughput sequencing, real-time PCR, Western blotting, Masson staining and bioinformatics analysis. Results:Through real-time PCR, Western blotting and Masson staining, a mouse model with cisplatin-induced renal interstitial fibrosis was successfully established. Through RNA Illumina high-throughput sequencing, 387 long noncoding RNA (lncRNA) and 2 427 mRNA were differently expressed between cisplatin group and saline group. The expression of the top two lncRNA was confirmed by real-time PCR with the same tendency as RNA sequencing. Complement C3 was found to be at the top among the different expressed mRNA by RNA sequencing. Several terms related to immunity were found to be within the top 20 terms through Gene Ontology (GO) enrichment analysis. Systemic lupus erythematous pathway (ko05322, Q=3.4E-17), including the complement cascade pathway, was found to be the top pathway through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA expression levels of C1q, C2, C3 and C4 were up-regulated remarkably in the cisplatin group by RNA sequencing than those in saline group (all P<0.05) and confirmed by real-time PCR. Conclusions:Renal interstitial fibrosis can be induced by intraperitoneal injection of cisplatin periodically in mice, with complement cascade pathway activation in the diseased kidney.
