P2 X 7 receptor is a critical regulator of extracellular ATP-induced profibrotic genes expression in rat kidney: implication of transforming growth factor-β/Smad signaling pathway.

IF 3 4区医学 Q2 NEUROSCIENCES

Purinergic Signalling Pub Date : 2024-08-01 Epub Date: 2023-11-07 DOI:10.1007/s11302-023-09977-4

Fatma Mounieb, Somaia A Abdel-Sattar, Amany Balah, El-Sayed Akool

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Abstract

This study was designed to investigate the potential of extracellular adenosine 5'-triphosphate (ATP) via the P2 X 7 receptor to activate the renal fibrotic processes in rats. The present study demonstrates that administration of ATP rapidly activated transforming growth factor-β (TGF-β) to induce phosphorylation of Smad-2/3. Renal connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA and protein expressions were also increased following ATP administration. A decrease in TGF-β amount in serum as well as renal Smad-2/3 phosphorylation was noticed in animals pre-treated with the specific antagonist of P2 X 7 receptor, A 438,079. In addition, a significant reduction in mRNA and protein expression of CTGF and TIMP-1were also observed in the kidneys of those animals. Collectively, the current findings demonstrate that ATP has the ability to augment TGF-β-mediated Smad-2/3 phosphorylation and enhance the expression of the pro-fibrotic genes, CTGF and TIMP-1, an effect that is largely mediated via P2 X 7 receptor.

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第2页十、 7受体是细胞外ATP诱导的大鼠肾脏促纤维化基因表达的关键调节因子：转化生长因子-β/Smad信号通路的意义。

本研究旨在研究细胞外5’-三磷酸腺苷（ATP）通过P2 十、 7受体激活大鼠肾纤维化过程。本研究表明，给予ATP可快速激活转化生长因子-β（TGF-β），诱导Smad-2/3磷酸化。肾结缔组织生长因子（CTGF）和金属蛋白酶组织抑制剂-1（TIMP-1）的mRNA和蛋白表达也在ATP给药后增加。在用P2特异性拮抗剂预处理的动物中，注意到血清中TGF-β的量以及肾脏Smad-2/3磷酸化的减少十、 7受体A 438079。此外，在这些动物的肾脏中还观察到CTGF和TIMP-1的mRNA和蛋白表达显著降低。总之，目前的研究结果表明，ATP有能力增强TGF-β介导的Smad-2/3磷酸化，并增强促纤维化基因CTGF和TIMP-1的表达，这种作用主要通过P2介导十、 7受体。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.