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

Overview

Journal Purinergic Signal

Publisher Springer

Date 2023 Nov 7

PMID 37934321

Authors

Fatma Mounieb

Somaia A Abdel-Sattar

Amany Balah

El-Sayed Akool

Affiliations

Soon will be listed here.

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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