Rodrigues Patrícia Garcia, Bringhenti Rafael Nazário, do Nascimento Jonathan Frapporti, Joelsons Gabriel, dos Santos Mariane, Pereira Sane, Veronese Francisco Veríssimo
Post-Graduate Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul Porto Alegre, RS, Brazil.
Division of Pathology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2185-98. eCollection 2014.
It is not clear how the podocyte damage manifests in different glomerulopathies. This study evaluated the podocyte-associated mRNA profiles in renal tissue and urine of patients with proliferative (PGs) or non-proliferative (NPGs) glomerulopathies.
Messenger RNA levels of nephrin, podocin, podocalyxin, synaptopodin, and alpha-actinin-4 were measured in the kidney tissue and urinary cells by real-time polymerase chain reaction. Podocyte-associated mRNAs were correlated with proteinuria and renal function, and the effect of immunosuppressive treatment of PGs and NPGs on urine mRNAs was assessed up to one year of follow up.
Podocyte-associated mRNAs were expressed consistently less in kidney tissue from patients with NPGs, and urinary podocyte mRNA levels were significantly higher in the PG group. After six months of immunosuppressive therapy, patients with PGs showed a significant reduction in the expression of podocin, podocalyxin, and alpha-actinin-4 compared with baseline (p<0.001). In the NPG group, alpha-actinin-4 levels decreased (p=0.008), and there was also a trend toward reduced podocalyxin mRNA (p=0.08). Urine podocyte-associated mRNAs correlated with the level of proteinuria at baseline and at six months, and there was a trend toward an inverse correlation between urinary mRNAs and kidney function at one year of follow up.
Podocyte-associated mRNAs were inhibited in kidney tissue concomitantly with their increase in urine in these patients with glomerulopathies. Different profiles of mRNA expression were seen, pointing to a higher degree of intra-renal podocytopenia in the NPGs and of podocyturia in the PGs. The immunosuppressive therapy effectively reduced the urinary levels of podocyte-associated mRNAs.
尚不清楚足细胞损伤在不同肾小球病中如何表现。本研究评估了增殖性肾小球病（PGs）或非增殖性肾小球病（NPGs）患者肾组织和尿液中与足细胞相关的mRNA谱。
通过实时聚合酶链反应测量肾组织和尿细胞中nephrin、podocin、podocalyxin、synaptopodin和α-辅肌动蛋白-4的信使RNA水平。将与足细胞相关的mRNA与蛋白尿和肾功能相关联，并在长达一年的随访中评估PGs和NPGs免疫抑制治疗对尿mRNA的影响。
NPGs患者肾组织中与足细胞相关的mRNA表达始终较低，而PG组尿足细胞mRNA水平显著更高。免疫抑制治疗6个月后，PGs患者与基线相比，podocin、podocalyxin和α-辅肌动蛋白-4的表达显著降低（p<0.001）。在NPG组中，α-辅肌动蛋白-4水平降低（p=0.008），podocalyxin mRNA也有降低趋势（p=0.08）。尿足细胞相关mRNA与基线及6个月时的蛋白尿水平相关，随访1年时尿mRNA与肾功能呈负相关趋势。
在这些肾小球病患者中，与足细胞相关的mRNA在肾组织中受到抑制，同时其在尿液中增加。观察到不同的mRNA表达谱，表明NPGs中肾内足细胞减少程度更高，而PGs中足细胞尿程度更高。免疫抑制治疗有效降低了尿中与足细胞相关的mRNA水平。
