ICAM-1 related long noncoding RNA is associated with progression of IgA nephropathy and fibrotic changes in proximal tubular cells

• Published in: Scientific reports 2022-06, Vol.12 (1), p.9645-9645, Article 9645
• Main Authors: Wen, Lu, Zhao, Zhanzheng, Li, Fanghua, Ji, Fengping, Wen, Jianguo
• Format: Article
• Language: English
• Subjects: 692/53/2422; 692/53/2423; 692/699/1585/104; 692/699/1585/104/1586; 692/699/1585/2759/1522; 692/699/1585/3182; AKT protein; Biomarkers; Biopsy; Cell adhesion; Collagen (type I); Disease Progression; End-stage renal disease; Fibrosis; Gene expression; Glomerular filtration rate; Glomerulonephritis, IGA - metabolism; Humanities and Social Sciences; Humans; IgA nephropathy; Immunoglobulin A; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Kidney diseases; multidisciplinary; Patients; Phosphorylation; Plasmids; Proteins; Reclassification; Risk factors; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Steroids; Survival analysis; TOR protein; Transfection; Transforming growth factor-b1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-13521-6

Intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) is on the antisense strand of ICAM-1 and regulates ICAM-1 expression. ICAM-1 is involved in renal tubulointerstitial injury; however, the expression and clinical implication of ICR are not determined in IgA nephropathy (IgAN). We compared renal ICR levels in 337 IgAN patients with those of 89 biopsy controls, and a markedly increased ICR level was observed in IgAN patients. By Cox proportional hazards models, higher levels of renal ICR were independently associated with disease progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the highest tertile of renal ICR had a 3.5-fold higher risk for disease progression compared with those in the lowest tertile. The addition of renal ICR to a model with traditional risk factors improved risk prediction of disease progression (net reclassification index: 0.31 [95% CI 0.01–0.50]; integrated discrimination index: 0.10 [95% CI 0.04–0.16]). Inhibition of ICR by transfection with plasmids containing ICR shRNA significantly reduced expression of collagen I and α-SMA, and phosphorylation of Akt and mTOR in TGF-β1- treated HK-2 cells. Our findings suggest that renal ICR might be an independent predictor of IgAN progression and contribute to renal fibrosis.