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Urinary podocyte-associated mRNA profile in various stages of diabetic nephropathy.

Zheng M, Lv LL, Ni J, Ni HF, Li Q, Ma KL, Liu BC - PLoS ONE (2011)

Bottom Line: Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers.Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = -0.349, p = 0.01).The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China.

ABSTRACT

Background: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.

Methods: DN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.

Results: The urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = -0.349, p = 0.01).

Conclusion: The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

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Comparison of podocyte-associated mRNA expressions in urinary between DN patients and health controls.Box plots show the minimum value, 25th, 50th (median), 75th, and the maximum values for lg-transformed ratios of mRNA copies compared with β-actin mRNA copies for synaptopodin, CD2-AP, α-actin4, podocin, and podocalyxin. Data were compared using the Mann-Whitney U test. DN  =  Diabetic nephropathy.
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pone-0020431-g001: Comparison of podocyte-associated mRNA expressions in urinary between DN patients and health controls.Box plots show the minimum value, 25th, 50th (median), 75th, and the maximum values for lg-transformed ratios of mRNA copies compared with β-actin mRNA copies for synaptopodin, CD2-AP, α-actin4, podocin, and podocalyxin. Data were compared using the Mann-Whitney U test. DN  =  Diabetic nephropathy.

Mentions: We first compared the levels of target gene expression between the DN groups and the healthy controls. Figure 1 summarizes the expression of the target genes synaptopodin, CD2-AP, α-actin4, podocin and podocalyxin in urinary sediment from all study subjects. The gene levels were compared by the log-transformed ratio of target gene mRNA to β-actin expression in urinary sediment cells. We found that all five target genes show significantly higher levels of expression in the experimental groups compared with the control group (p = 0.007 for synaptopodin, p = 0.047 for CD2-AP,p = 0.01 for α-actin4, p = 0.006 for podocalyxin, and p = 0.021 for podocin, respectively, by Mann-Whitney test).


Urinary podocyte-associated mRNA profile in various stages of diabetic nephropathy.

Zheng M, Lv LL, Ni J, Ni HF, Li Q, Ma KL, Liu BC - PLoS ONE (2011)

Comparison of podocyte-associated mRNA expressions in urinary between DN patients and health controls.Box plots show the minimum value, 25th, 50th (median), 75th, and the maximum values for lg-transformed ratios of mRNA copies compared with β-actin mRNA copies for synaptopodin, CD2-AP, α-actin4, podocin, and podocalyxin. Data were compared using the Mann-Whitney U test. DN  =  Diabetic nephropathy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105067&req=5

pone-0020431-g001: Comparison of podocyte-associated mRNA expressions in urinary between DN patients and health controls.Box plots show the minimum value, 25th, 50th (median), 75th, and the maximum values for lg-transformed ratios of mRNA copies compared with β-actin mRNA copies for synaptopodin, CD2-AP, α-actin4, podocin, and podocalyxin. Data were compared using the Mann-Whitney U test. DN  =  Diabetic nephropathy.
Mentions: We first compared the levels of target gene expression between the DN groups and the healthy controls. Figure 1 summarizes the expression of the target genes synaptopodin, CD2-AP, α-actin4, podocin and podocalyxin in urinary sediment from all study subjects. The gene levels were compared by the log-transformed ratio of target gene mRNA to β-actin expression in urinary sediment cells. We found that all five target genes show significantly higher levels of expression in the experimental groups compared with the control group (p = 0.007 for synaptopodin, p = 0.047 for CD2-AP,p = 0.01 for α-actin4, p = 0.006 for podocalyxin, and p = 0.021 for podocin, respectively, by Mann-Whitney test).

Bottom Line: Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers.Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = -0.349, p = 0.01).The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China.

ABSTRACT

Background: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.

Methods: DN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.

Results: The urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = -0.349, p = 0.01).

Conclusion: The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

Show MeSH
Related in: MedlinePlus