Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study

Abstract Chronic kidney disorder is a rising danger to health that affects a significant percentage of older adults, and a crucial stage in its development is fibrosis. MicroRNAs and transforming_ growth factor-β1(TGF-β1) /SMAD2 signal pathway significantly regulate this process. miR-34a promotes ex...

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Main Authors: Yosra M. Magdy, Sherif A. Kamar, Tamer M. M. Abuamara, Yomna M. Tamim, Hayam Ateyya, Marwa Tarek, Nehal Samir, Reham Hussein
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:Future Journal of Pharmaceutical Sciences
Subjects:
Online Access:https://doi.org/10.1186/s43094-025-00829-z
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author Yosra M. Magdy
Sherif A. Kamar
Tamer M. M. Abuamara
Yomna M. Tamim
Hayam Ateyya
Marwa Tarek
Nehal Samir
Reham Hussein
author_facet Yosra M. Magdy
Sherif A. Kamar
Tamer M. M. Abuamara
Yomna M. Tamim
Hayam Ateyya
Marwa Tarek
Nehal Samir
Reham Hussein
author_sort Yosra M. Magdy
collection DOAJ
description Abstract Chronic kidney disorder is a rising danger to health that affects a significant percentage of older adults, and a crucial stage in its development is fibrosis. MicroRNAs and transforming_ growth factor-β1(TGF-β1) /SMAD2 signal pathway significantly regulate this process. miR-34a promotes extracellular matrix (ECM) deposition and inhibits B cell lymphoma-2 (Bcl-2), a target gene with antifibrotic properties shown to protect against renal fibrosis in animal models. Currently, several drugs, including entacapone, have been reported to suppress miR-34a activation. Experimental model of Carbon- tetrachloride (CCl4)-induced renal fibrosis revealed elevated serum levels of urea and creatinine, an increased urinary microalbumin-to-creatinine ratio, deterioration of the antioxidant-oxidant balance, an increase in TGF-β1 in renal tissue, and increased renal miR–34a–SMAD2 expression were observed, accompanied by decreased expression of Bcl-2. Entacapone holds reno-protective promises likely via its anti-inflammatory-antioxidant effects in CCl4-induced renal fibrosis by favorable modulation of miR-34a /TGF-β1/SMAD2 Signaling Pathway.
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spelling doaj-art-ddbbb13a15ed400b9db8656f1206e11c2025-08-20T02:40:15ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532025-06-0111111310.1186/s43094-025-00829-zEntacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model studyYosra M. Magdy0Sherif A. Kamar1Tamer M. M. Abuamara2Yomna M. Tamim3Hayam Ateyya4Marwa Tarek5Nehal Samir6Reham Hussein7Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams UniversityDepartment of Basic Medical Sciences, Faculty of Dentistry, Al-Ahliyya Amman University (AAU)Department of Basic Medical Sciences, Faculty of Dentistry, Al-Ahliyya Amman University (AAU)Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams UniversityDepartment of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Future University in EgyptDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams UniversityDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams UniversityDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams UniversityAbstract Chronic kidney disorder is a rising danger to health that affects a significant percentage of older adults, and a crucial stage in its development is fibrosis. MicroRNAs and transforming_ growth factor-β1(TGF-β1) /SMAD2 signal pathway significantly regulate this process. miR-34a promotes extracellular matrix (ECM) deposition and inhibits B cell lymphoma-2 (Bcl-2), a target gene with antifibrotic properties shown to protect against renal fibrosis in animal models. Currently, several drugs, including entacapone, have been reported to suppress miR-34a activation. Experimental model of Carbon- tetrachloride (CCl4)-induced renal fibrosis revealed elevated serum levels of urea and creatinine, an increased urinary microalbumin-to-creatinine ratio, deterioration of the antioxidant-oxidant balance, an increase in TGF-β1 in renal tissue, and increased renal miR–34a–SMAD2 expression were observed, accompanied by decreased expression of Bcl-2. Entacapone holds reno-protective promises likely via its anti-inflammatory-antioxidant effects in CCl4-induced renal fibrosis by favorable modulation of miR-34a /TGF-β1/SMAD2 Signaling Pathway.https://doi.org/10.1186/s43094-025-00829-zBcl-2CCl4EntacaponemiR-34aOxidative stressRenal fibrosis
spellingShingle Yosra M. Magdy
Sherif A. Kamar
Tamer M. M. Abuamara
Yomna M. Tamim
Hayam Ateyya
Marwa Tarek
Nehal Samir
Reham Hussein
Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
Future Journal of Pharmaceutical Sciences
Bcl-2
CCl4
Entacapone
miR-34a
Oxidative stress
Renal fibrosis
title Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
title_full Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
title_fullStr Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
title_full_unstemmed Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
title_short Entacapone’s therapeutic potential in renal fibrosis by targeting miR-34a/TGFβ1/Smad2 signaling: an experimental rat model study
title_sort entacapone s therapeutic potential in renal fibrosis by targeting mir 34a tgfβ1 smad2 signaling an experimental rat model study
topic Bcl-2
CCl4
Entacapone
miR-34a
Oxidative stress
Renal fibrosis
url https://doi.org/10.1186/s43094-025-00829-z
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