Abstract: PO1903
Complement Activation in a Mouse Model of Cisplatin-Induced Renal Interstitial Fibrosis
Session Information
- Cancer-Related Kidney Injury: Paraneoplastic Syndromes and More
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Feng, Min, Department of Nephrology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Su, Jianan, Department of Nephrology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Zeng, Honghui, Medical Research Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Background
Cisplatin is widely used for tumor chemotherapy. Renal interstitial fibrosis and chronic renal failure could be induced by periodic use of cisplatin. The mechanism of cisplatin induced renal interstitial fibrosis needs to be clarified.
Methods
In cisplatin group, male C57BL/6 mice were intraperitoneal injected with cisplatin(10mg/kg) on day 0, 7 and 21, and killed on day 28. In control group, mice were intraperitoneal injected with saline and killed at the same timepoint as cisplatin group. The kidney tissue was collected for RNA Illumina high-throughput sequencing, real-time PCR, western blot and masson staining.
Results
Through real-time PCR, western blot and masson staining, successful establishment of a mouse model with cisplatin induced renal interstitial fibrosis was confirmed. Through RNA high-throughput sequencing, 387 long noncoding RNAs(lncRNAs) and 2427 mRNAs were differently expressed between cisplatin group and control group. The expression of lncRNA MSTRG.8677 and lncRNA MSTRG.405 were verified by real-time PCR with the same tendency as RNA sequencing. Complement C3 was found to be at the top among the different expressed mRNAs by RNA sequencing. Several terms related to immunity were found to be within the top 20 terms through GO enrichment analysis of different expressed mRNAs. Systemic lupus erythematous pathway(ko05322,Q=3.4e-17), including the complement cascade pathway, was found to be the top pathway through KEGG enrichment analysis of different expressed mRNAs. The mRNA expression of C3,C1q,C2 and C4 were found to upregulated remarkably in cisplatin group by RNA sequencing and verified by real-time PCR.
Conclusion
Renal interstitial fibrosis could be induced by intraperitoneal injection of cisplatin periodically in mice, with complement cascade pathway activation in the diseased kidney.
Funding
- Other NIH Support