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长链非编码 RNA RPL29P2 通过 miR-1184 在腹膜透析中促进腹膜纤维化并损害腹膜转运功能。

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

机构信息

Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.

Department of Nephrology, the Second People's Hospital of Shaan xi Province, Xi'an, Shaanxi, China.

出版信息

Int J Med Sci. 2024 Apr 15;21(6):1049-1063. doi: 10.7150/ijms.93547. eCollection 2024.

DOI:10.7150/ijms.93547
PMID:38774747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11103403/
Abstract

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

摘要

腹膜透析 (PD)、血液透析和肾移植是治疗尿毒症的三种疗法。然而，由于 PD 液（PDF）中高浓度葡萄糖对腹膜的损伤，PD 会因腹膜膜纤维化 (PMF) 和腹膜转运功能丧失 (PTF) 而停止。PMF 的发病机制尚不清楚，也没有可用的生物标志物来评估 PMF 和 PTF。通过微阵列筛选，我们发现一种新的长非编码 RNA (lncRNA)，RPL29P2，在长期 PD 患者的 PM（腹膜）中上调，其表达水平与 PMF 严重程度和 PTF 丧失相关。大鼠模型试验表明，lncRNA RPL29P2 靶向 miR-1184，并诱导胶原 I 型α 1 链 (COL1A1) 的表达。在 PD 大鼠模型中沉默 RPL29P2 可能抑制 HG 诱导的人腹膜间皮细胞 (HPMCs) 的表型转化，减轻 HG 诱导的纤维化并防止 PTF 丧失。总的来说，我们的研究结果表明，lncRNA RPL29P2 靶向 miR-1184 和胶原，可能代表 PD 患者 PMF 的一个有用的标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fba/11103403/d699a31be307/ijmsv21p1049g006.jpg
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