Journal
SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-13521-6
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Funding
- National Natural Science Foundation of China [U1904208]
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Increased levels of renal ICR are independently associated with disease progression in IgA nephropathy and improve risk prediction of disease progression.
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 alpha-SMA, and phosphorylation of Akt and mTOR in TGF-beta 1- treated HK-2 cells. Our findings suggest that renal ICR might be an independent predictor of IgAN progression and contribute to renal fibrosis.
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