TGF-β and Wnt Pathways Underlying the Pathophysiology of Degenerative Mitral Valve Regurgitation

Günseli Çubukçuoğlu Deniz

Makale detayları

TGF-β and Wnt Pathways Underlying the Pathophysiology of Degenerative Mitral Valve Regurgitation

Yazarlar:

Günseli Çubukçuoğlu Deniz

Yayıncı:

Ankara University

Ana Başlıklar:

Cell Physiology

Dergi:

Ankara Üniversitesi Tıp Fakültesi Mecmuası Vol.77 Issue 4, pp.410-415

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001349736

pISSN:

0365-8104

Anahtar kelimeler:

Özet:

 Objectives: In aging society, hospitalizations and mitral valve surgeries are becoming more common due to progressive mitral valve diseases that ultimately lead to heart failure. In developing countries, degenerative mitral valve regurgitation DMVR is the leading cause of mitral regurgitation requiring surgical treatment. Nevertheless, a more profound understanding of the underlying pathological processes via a molecular biology approach could improve clinical management. In this study, bioinformatic analyses were performed to elucidate the underlying pathophysiological molecular mechanisms using transcriptome data of atrial tissues from patients with DMVR. Materials and Methods: Bioinformatic analysis were done using GSE115574 dataset from The Gene Expression Omnibus GEO database. Transcriptome data which were downloaded from GEO database in CEL files generated from human left atrium and right atrium tissues in patients with DMVR in sinus rhythm n16 was used to perform bioinformatic analysis. Gene expression microarray analysis have done on Affymetrix platform previously. Bioinformatics, gene ontology, and functional enrichment analysis have been conducted on Partek GS V7.0 and WebGestalt software. Results: The findings of this study reveal that multiple genes and various pathways play a role in the pathophysiology of DMVR. Among all transforming growth factor-beta TGF-β and Wnt signaling pathways enlightened according to false discovery rate thresholds and enriched geneset values. Prominent genes that involved in TGF-β and Wnt signaling pathways were WNT5A, PLCB1, SFRP1, SMAD6, PITX2, SMAD7, ID2, BMP5. Conclusion: Its important to crystallize the molecular mechanisms of DMVR to facilitate early detection and develop targeted interventions. Management of TGF-β and Wnt signaling pathways in correct direction may offer solutions to slow DMVR progression and prevent it from becoming more complex.

 Objectives: In aging society, hospitalizations and mitral valve surgeries are becoming more common due to progressive mitral valve diseases that ultimately lead to heart failure. In developing countries, degenerative mitral valve regurgitation DMVR is the leading cause of mitral regurgitation requiring surgical treatment. Nevertheless, a more profound understanding of the underlying pathological processes via a molecular biology approach could improve clinical management. In this study, bioinformatic analyses were performed to elucidate the underlying pathophysiological molecular mechanisms using transcriptome data of atrial tissues from patients with DMVR. Materials and Methods: Bioinformatic analysis were done using GSE115574 dataset from The Gene Expression Omnibus GEO database. Transcriptome data which were downloaded from GEO database in CEL files generated from human left atrium and right atrium tissues in patients with DMVR in sinus rhythm n16 was used to perform bioinformatic analysis. Gene expression microarray analysis have done on Affymetrix platform previously. Bioinformatics, gene ontology, and functional enrichment analysis have been conducted on Partek GS V7.0 and WebGestalt software. Results: The findings of this study reveal that multiple genes and various pathways play a role in the pathophysiology of DMVR. Among all transforming growth factor-beta TGF-β and Wnt signaling pathways enlightened according to false discovery rate thresholds and enriched geneset values. Prominent genes that involved in TGF-β and Wnt signaling pathways were WNT5A, PLCB1, SFRP1, SMAD6, PITX2, SMAD7, ID2, BMP5. Conclusion: Its important to crystallize the molecular mechanisms of DMVR to facilitate early detection and develop targeted interventions. Management of TGF-β and Wnt signaling pathways in correct direction may offer solutions to slow DMVR progression and prevent it from becoming more complex.

 Objectives: In aging society, hospitalizations and mitral valve surgeries are becoming more common due to progressive mitral valve diseases that ultimately lead to heart failure. In developing countries, degenerative mitral valve regurgitation DMVR is the leading cause of mitral regurgitation requiring surgical treatment. Nevertheless, a more profound understanding of the underlying pathological processes via a molecular biology approach could improve clinical management. In this study, bioinformatic analyses were performed to elucidate the underlying pathophysiological molecular mechanisms using transcriptome data of atrial tissues from patients with DMVR. Materials and Methods: Bioinformatic analysis were done using GSE115574 dataset from The Gene Expression Omnibus GEO database. Transcriptome data which were downloaded from GEO database in CEL files generated from human left atrium and right atrium tissues in patients with DMVR in sinus rhythm n16 was used to perform bioinformatic analysis. Gene expression microarray analysis have done on Affymetrix platform previously. Bioinformatics, gene ontology, and functional enrichment analysis have been conducted on Partek GS V7.0 and WebGestalt software. Results: The findings of this study reveal that multiple genes and various pathways play a role in the pathophysiology of DMVR. Among all transforming growth factor-beta TGF-β and Wnt signaling pathways enlightened according to false discovery rate thresholds and enriched geneset values. Prominent genes that involved in TGF-β and Wnt signaling pathways were WNT5A, PLCB1, SFRP1, SMAD6, PITX2, SMAD7, ID2, BMP5. Conclusion: Its important to crystallize the molecular mechanisms of DMVR to facilitate early detection and develop targeted interventions. Management of TGF-β and Wnt signaling pathways in correct direction may offer solutions to slow DMVR progression and prevent it from becoming more complex.

 Amaç: Yaşlanan toplumlarda, en nihayetinde kalp yetmezliğine ilerleyen progresif mitral kapak hastalıkları nedeniyle hastaneye yatışlar ve mitral kapak ameliyatları daha yaygın hale gelmiştir. Gelişmekte olan ülkelerde, dejeneratif mitral kapak yetersizliği DMVR cerrahi tedavi gerektiren mitral yetersizliğinin önde gelen nedenidir. Bununla birlikte, altta yatan patolojik süreçlerin moleküler biyoloji yaklaşımıyla daha derinlemesine anlaşılması klinik yönetimi iyileştirebilir. Bu araştırmada, DMVRli hastalardan alınan atriyum dokularının transkriptom verisi kullanılarak, altta yatan patofizyolojik moleküler mekanizmaları aydınlatmak amacıyla biyoinformatik analizler yapılmıştır. Gereç ve Yöntem: Biyoinformatik analizler, Gen Ekspresyon Omnibus GEO veritabanından GSE115574 veriseti kullanılarak gerçekleştirilmiştir. Sinüs ritmindeki DMVR hastalarında n16 insan sol atriyum ve sağ atriyum elde edilen ve GEO veritabanından CEL dosyaları olarak indirilen transkriptom verisi biyoinformatik analizleri yapmak için kullanılmıştır. Gen ekspresyon mikroarray analizleri daha öncesinde Affymetrix platformunda gerçekleştirilmiştir. Biyoinformatik, gen ontolojisi ve fonksiyonel zenginleştirme analizleri Partek GS V7.0 ve WebGestalt yazılımlarında gerçekleştirilmiştir. Bulgular: Bu çalışmanın bulguları, DMVR patofizyolojisinde birden fazla genin ve çeşitli yolakların rol oynadığını ortaya koymaktadır. Tüm dönüştürücü büyüme faktörü-beta TGF-β ve Wnt sinyal yolakları arasında yanlış keşif oranı eşiklerine ve zenginleştirilmiş gen seti değerlerine göre aydınlatılmıştır. TGF-β ve Wnt sinyal yolaklarında yer alan öne çıkan genler WNT5A, PLCB1, SFRP1, SMAD6, PITX2, SMAD7, ID2, BMP5 olarak tespit edilmiştir. Sonuç: Erken teşhisi kolaylaştırmak ve hedefe yönelik müdahaleler geliştirmek için DMVRnin moleküler mekanizmalarının tam olarak aydınlatılması önemlidir. TGF-β ve Wnt sinyal yolaklarının doğru şekilde yönetilmesi, DMVR progresyonunu yavaşlatmak ve daha karmaşık hale gelmesini önlemek için çözümler sunabilir.

Makale detayları

TGF-β and Wnt Pathways Underlying the Pathophysiology of Degenerative Mitral Valve Regurgitation

Yazarlar:

Günseli Çubukçuoğlu Deniz

Yayıncı:

Ankara University

Ana Başlıklar:

Cell Physiology

Dergi:

Ankara Üniversitesi Tıp Fakültesi Mecmuası Vol.77 Issue 4, pp.410-415

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001349736

pISSN:

0365-8104

Mitral valve

TGF-β signaling pathway

Wnt signaling pathwayMitral kapak

TGF-β sinyal yolağı

Wnt sinyal yolağı

Sayı

Makale detayları

TGF-β and Wnt Pathways Underlying the Pathophysiology of Degenerative Mitral Valve Regurgitation

Yazarlar: Günseli Çubukçuoğlu Deniz

Yayıncı: Ankara University

Ana Başlıklar: Cell Physiology

Dergi: Ankara Üniversitesi Tıp Fakültesi Mecmuası Vol.77 Issue 4, pp.410-415

Belge Tipi: Makale

Yayın Tarihi: 12/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001349736

pISSN: 0365-8104

Mitral valve

TGF-β signaling pathway

Wnt signaling pathwayMitral kapak

TGF-β sinyal yolağı

Wnt sinyal yolağı

Sayı

Yazarlar:

Günseli Çubukçuoğlu Deniz

Yayıncı:

Ankara University

Ana Başlıklar:

Cell Physiology

Dergi:

Ankara Üniversitesi Tıp Fakültesi Mecmuası Vol.77 Issue 4, pp.410-415

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001349736

pISSN:

0365-8104