Let-7c-5p Is Involved in Chronic Kidney Disease by Targeting TGF-β Signaling

الملخص EN

The purpose of the present study was to investigate the expressions of hsa-let-7c-5p and TGF-β signaling-related molecules and their correlations with clinical characteristics in chronic kidney disease (CKD).

Twenty-three biopsy specimens of CKD patients and 20 negative control tissues were selected.

Quantitative real-time PCR (qPCR) was used for the detection of hsa-let-7c-5p, transforming growth factor β (TGF-β) and TGF-β receptor type 1 (TGF-βR1) expression levels.

Target gene of hsa-let-7c-5p was verified by dual-luciferase reporter assay.

A significant decrease of hsa-let-7c-5p expression in CKD tissue was found, compared with that of normal renal tissues (p<0.01).

Expression levels of TGF-β in CKD were increased, compared with that of normal kidney tissue (p<0.001).

The difference in the expression of TGF-β R1 between CKD tissues and normal renal tissues was not significant (p>0.05).

A negative correlation was found between the expression of TGF-β and renal tissue hsa-let-7c-5p levels.

Furthermore, hsa-let-7c-5p was identified to regulate TGF- β1 by directly binding with the 167-173 site in the 3′ untranslated region.

Decreased hsa-let-7c-5p levels in CKD patients was found to be associated with disease severity, which shows a negative correlation with proteinuria and creatinine levels, and a positive correlation with estimated glomerular filtration rate (eGFR), while relative TGF-β1 expression had a positive correlation with creatinine level.

In summary, changes in hsa-let-7c-5p expression and its target gene TGF-β are associated with the disease status of CKD.

Let-7c-5p may contribute to the pathogenesis of renal fibrosis through TGF-β signaling, a potential diagnostic and therapeutic target of the disease.