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

Zhenguo Wang1, Cuixing Zhou1, Yangyang Sun1

  • 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.

Biomed Research International
|July 7, 2020
PubMed

Insights

Reduced hsa-let-7c-5p expression correlates with chronic kidney disease (CKD) severity. This microRNA may drive renal fibrosis via TGF-β signaling, offering potential diagnostic and therapeutic targets for CKD.

Area of Science:

  • Molecular Biology
  • Nephrology
  • Biochemistry

Background:

  • Chronic kidney disease (CKD) is a progressive condition characterized by declining kidney function.
  • Transforming growth factor-beta (TGF-β) signaling is implicated in the pathogenesis of renal fibrosis, a hallmark of CKD.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are increasingly recognized for their roles in disease.

Purpose of the Study:

  • To investigate the expression levels of hsa-let-7c-5p and TGF-β signaling molecules in CKD.
  • To explore the correlation between hsa-let-7c-5p, TGF-β signaling, and clinical characteristics in CKD patients.
  • To elucidate the regulatory relationship between hsa-let-7c-5p and TGF-β1.

Main Methods:

  • Quantitative real-time PCR (qPCR) to measure hsa-let-7c-5p, TGF-β, and TGF-β receptor type 1 (TGF-βR1) expression.
  • Dual-luciferase reporter assay to confirm the target gene of hsa-let-7c-5p.
  • Analysis of correlations between molecular expression and clinical parameters like proteinuria, creatinine, and estimated glomerular filtration rate (eGFR).

Main Results:

  • CKD tissues showed significantly decreased hsa-let-7c-5p expression compared to normal renal tissues (p < 0.01).
  • TGF-β expression was significantly increased in CKD tissues (p < 0.001), while TGF-βR1 showed no significant difference.
  • hsa-let-7c-5p directly targets and regulates TGF-β1, with decreased hsa-let-7c-5p correlating negatively with proteinuria and creatinine, and positively with eGFR.

Conclusions:

  • Downregulation of hsa-let-7c-5p is associated with CKD progression and severity.
  • The hsa-let-7c-5p/TGF-β1 axis plays a role in the pathogenesis of renal fibrosis in CKD.
  • hsa-let-7c-5p and TGF-β signaling represent potential diagnostic biomarkers and therapeutic targets for CKD.

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