Adenosine A1 Receptor Deficiency Aggravates Extracellular Matrix Accumulation in Diabetic Nephropathy through Disturbance of Peritubular Microenvironment.
Adenosine A1 Receptor Deficiency Aggravates Extracellular Matrix Accumulation in Diabetic Nephropathy through Disturbance of Peritubular Microenvironment.
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腺苷A1受体缺乏可通过周围微环境扰动糖尿病性肾病中的细胞外基质积累。
DOI：
10.1155/2021/5584871
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发表时间：
2021
影响因子：
4.3
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Tian D;Li J;Zou L;Lin M;Shi X;Hu Y;Lang J;Xu L;Ye W;Li X;Chen L
我们先前观察到腺苷A1受体（A1 AR）在糖尿病肾病（DN）中与蛋白尿相关的近端肾小管巨蛋白丢失中具有保护作用。本研究旨在探讨A1 AR在DN纤维化进展中的作用。 我们收集了DN患者的样本，并在野生型（WT）和A1 AR缺陷型（A1 AR −/−）小鼠中建立了链脲佐菌素诱导的糖尿病模型。采用免疫荧光和免疫组化染色方法检测DN患者肾组织中CD 34、PDGFRβ和A1 AR的定位和表达。我们还使用免疫组织化学分析了WT和A1 AR −/−小鼠中TGFβ、胶原（I、III和IV）、α-SMA和PDGFRβ的表达。免疫印迹和免疫组织化学染色分别检测CD 34和podoplanin的表达。人肾小管上皮细胞（HK 2）在高糖及A1 AR激动剂和拮抗剂的培养基中培养。 在DN患者中，PDGFRβ的表达随着CD 34的丢失而增加。PDGFRβ和TGFβ的表达位置接近。与CD 34部分共定位的A1 AR在DN患者中也上调。WT-DN小鼠出现明显的蛋白尿和肾脏病理休闲。在A1 AR −/− DN小鼠中，观察到更严重的肾小管间质纤维化和更多的细胞外基质沉积，CD 34表达降低，PDGFRβ显著增加。在HK 2细胞中，高糖刺激上皮-间质转化（EMT）过程，这是由A1 AR激动剂抑制。 A1 AR通过调节肾小管周围微环境，在DN肾小管间质纤维化过程中发挥重要作用。
We previously observed that adenosine A1 receptor (A1AR) had a protective role in proximal tubular megalin loss associated with albuminuria in diabetic nephropathy (DN). In this study, we aimed to explore the role of A1AR in the fibrosis progression of DN. We collected DN patients' samples and established a streptozotocin-induced diabetes model in wild-type (WT) and A1AR-deficient (A1AR−/−) mice. The location and expression of CD34, PDGFRβ, and A1AR were detected in kidney tissue samples from DN patients by immunofluorescent and immunohistochemical staining. We also analyzed the expression of TGFβ, collagen (I, III, and IV), α-SMA, and PDGFRβ using immunohistochemistry in WT and A1AR−/− mice. CD34 and podoplanin expression were analyzed by Western blotting and immunohistochemical staining in mice, respectively. Human renal proximal tubular epithelial cells (HK2) were cultured in medium containing high glucose and A1AR agonist as well as antagonist. In DN patients, the expression of PDGFRβ was higher with the loss of CD34. The location of PDGFRβ and TGFβ was near to each other. The A1AR, which was colocalized with CD34 partly, was also upregulated in DN patients. In WT-DN mice, obvious albuminuria and renal pathological leisure were observed. In A1AR−/− DN mice, more severe renal tubular interstitial fibrosis and more extracellular matrix deposition were observed, with lower CD34 expression and pronounced increase of PDGFRβ. In HK2 cells, high glucose stimulated the epithelial-mesenchymal transition (EMT) process, which was inhibited by A1AR agonist. A1AR played a critical role in protecting the tubulointerstitial fibrosis process in DN by regulation of the peritubular microenvironment.
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影响因子：
3.7
作者：
Kretschmar C;Oyarzún C;Villablanca C;Jaramillo C;Alarcón S;Perez G;Díaz-Encarnación MM;Pastor-Anglada M;Garrido W;Quezada C;San Martín R
通讯作者：
San Martín R
影响因子：
13.6
作者：
Faulhaber-Walter, Robert;Chen, Limeng;Schnermann, Jurgen
通讯作者：
Schnermann, Jurgen
影响因子：
6
作者：
Lin, Shuei-Liong;Kisseleva, Tatiana;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
DOI：
10.1152/ajprenal.00030.2016
发表时间：
2016-12-01
影响因子：
4.2
作者：
Lemos, Dario R.;Marsh, Graham;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
影响因子：
19.6
作者：
Kim, Minjae;Chen, Sean W. C.;Park, Sang Won;Kim, Mihwa;D'Agati, Vivette D.;Yang, Jay;Lee, H. Thomas
通讯作者：
Lee, H. Thomas