Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy

BMC Genomics

Xiaosong Qin¹  Yibo Bai¹  Shixiao Chen¹  Qiuying Liu¹  Baoxu Lin¹  Yabin Wu¹  Jianhua Liu¹  Yue Zhang¹ 

[1] Department of Laboratory Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, 110004, Shenyang, P. R. China;

关键词: Urinary peptidomics;    Idiopathic membranous nephropathy;    Proteases;   

DOI  :  10.1186/s12864-021-08155-3

来源: Springer

【 摘 要 】

BackgroundIdiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases.ResultsPeptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN.ConclusionsThis work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.

【 授权许可】

CC BY