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MicroRNA In situ Hybridization for Formalin Fixed Kidney Tissues
Published on: November 30, 2013
Altered Expression of MicroRNAs Following Chronic Allograft Dysfunction with Interstitial Fibrosis and Tubular
Ehsan Soltaninejad1, Mohammad Hossein Nicknam2, Mohsen Nafar3
1Department of Immunology, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Chronic allograft dysfunction (CAD) remains the major cause of renal transplant loss and characterized by interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are implicated in many biological processes as well as innate and adaptive immune responses. We aimed to investigate whether CAD with IFTA is associated with differential expression of miR-142-5p, miR-142-3p and miR-211 within biopsy and peripheral blood mononuclear cell (PBMC) samples and whether expression of miRNAs are diagnostic for CAD with IFTA and predicts renal allograft function. In this study, biopsy and PBMC samples of 16 CAD with IFTA and 17 normal allografts (NA) were collected. Using Taqman MicroRNA Assays the expression levels of miR-142-5p, miR-142-3p and miR-211 were determined in two groups. Our results showed that miR-142-5p and miR-142-3p were significantly (p<0.0001) up-regulated and miR-211 was significantly (p<0.0001) down-regulated in renal allograft tissues of CAD with IFTA compared with NA recipients. Moreover, miR-142-3p and miR-211 were significantly (p<0.0001) up-regulated and down-regulated respectively in PBMC samples of CAD with IFTA. According to the ROC curve analysis, miR-142-5p in biopsy samples, but miR-142-3p and miR-211 both in biopsy and PBMC samples could be used as a diagnostic biomarker of CAD with IFTA and a prediction factor of allograft function. In this study, miRNAs were differentially expressed in the kidney allograft biopsy and simultaneously in PBMC samples of patients with CAD with IFTA. We suggest that the expression of miRNAs in PBMC might be used for monitoring the post transplantation and also as potential non-invasive biomarkers of kidney graft function and CAD with IFTA.
Insights
Specific microRNAs (miRNAs) show altered expression in kidney transplant biopsies and blood samples from patients with chronic allograft dysfunction (CAD) and interstitial fibrosis and tubular atrophy (IFTA). These miRNAs could serve as biomarkers for diagnosing CAD and predicting graft function.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Chronic allograft dysfunction (CAD) is the primary cause of renal transplant failure, characterized by interstitial fibrosis and tubular atrophy (IFTA).
- MicroRNAs (miRNAs) play crucial roles in biological processes, including immune responses, and are potential regulators of transplant outcomes.
Purpose of the Study:
- To investigate differential expression of miR-142-5p, miR-142-3p, and miR-211 in renal allograft biopsies and peripheral blood mononuclear cells (PBMCs) from patients with CAD and IFTA.
- To determine if these miRNA expressions can serve as diagnostic biomarkers for CAD with IFTA and predict renal allograft function.
Main Methods:
- Samples from 16 CAD with IFTA patients and 17 normal allograft recipients were analyzed.
- Taqman MicroRNA Assays were used to quantify the expression levels of miR-142-5p, miR-142-3p, and miR-211 in both biopsy and PBMC samples.
- Receiver Operating Characteristic (ROC) curve analysis was performed to assess diagnostic and predictive capabilities.
Main Results:
- miR-142-5p and miR-142-3p were significantly upregulated in renal allograft tissues of CAD with IFTA patients compared to normal allografts (p<0.0001).
- miR-211 was significantly downregulated in renal allograft tissues (p<0.0001).
- In PBMCs, miR-142-3p was significantly upregulated and miR-211 was significantly downregulated (p<0.0001).
- ROC analysis indicated miR-142-5p (biopsy), and miR-142-3p and miR-211 (both biopsy and PBMC) are potential diagnostic biomarkers for CAD with IFTA and predictors of allograft function.
Conclusions:
- Differential expression of miR-142-5p, miR-142-3p, and miR-211 occurs in both kidney allograft biopsies and PBMCs of patients with CAD and IFTA.
- PBMC-derived miRNAs show promise as non-invasive biomarkers for monitoring post-transplant status and predicting kidney graft function and CAD.
- These findings suggest potential for using circulating miRNAs as accessible biomarkers for kidney transplant management.

