Neonatal Kalp Rejenerasyonu: Hippo Sinyal Yolağı’nın Rolü

Yıl 2022, , 28 - 34, 31.03.2022

Yasemin Özküçük , Abdullah Tuli

https://doi.org/10.17827/aktd.1030555

Öz

Organ rejenerasyonu, hayvanlar aleminde yaygın olarak görülmekle birlikte insanlarda da karaciğer hasarından sonra meydana gelebilir. Bugüne kadar, kardiyak rejenerasyona yönelik klinik çalışmalarda hücre temelli tedavilere odaklanılmıştır. Ancak bu tedavilerin kardiyak fonksiyon üzerindeki etkisi ihmal edilebilir düzeyde olduğundan memelilerde kardiyak rejenerasyonu düzenleyen mekanizmalar üzerinde çalışmalar hız kazanmıştır. Zebra balığının (Danio rerio) endojen kalp rejenerasyonundan elde edilen bilgiler, karmaşık organ rejenerasyonu için doğuştan gelen mekanizmalara yeni bir anlayış kazandırmaktadır. Yapılan çalışmalar memeli neonatal kalplerinin de Zebra balıklarına benzer şekilde rejenerasyon kapasitesinin bulunduğunu, ancak bu rejeneratif kapasitenin doğum sonrası ilk birkaç günle sınırlı olduğunu göstermiştir. Bu süreçte rol oynayan pek çok moleküler ve hücresel mekanizma tanımlanmış olmasına karşın, en büyük ilgiyi Hippo sinyal yolağı görmüştür. Bu yolağın aktivitesi YAP’ın çekirdek/sitoplazmik lokalizasyonuna bağlı olup, ROS, ECM ve miRNA’lar gibi bir dizi moleküler faktör tarafından kontrol edilmektedir. Son birkaç yılda Hippo yolağının kardiyomiyosit hücre döngüsü üzerine etkilerini inceleyen araştırmalar, bu yolağın bileşenlerinin yetişkinlerde kardiyak rejenerasyon için umut verici olduğunu göstermiştir. Bu derlemeyle yetişkin memeli kalp dokusunda hasarın geri döndürülmesindeki önemli yeriyle yeni terapötik hedeflerin geliştirilmesinde önemli rolü olduğunu düşündüğümüz Hippo yolağı ve yolağın bileşenleri hakkında bilgi verilmesi amaçlanmıştır.

Anahtar Kelimeler

Organ rejenerasyonu, Kalp rejenerasyonu, Hippo yolu.

Neonatal Heart Regeneration: The Role of the Hippo Signaling Pathway

Öz

Although organ regeneration is common in the animal kingdom, it can also occur in humans after liver injury. To date, in the clinical trials for cardiac regeneration have been focused on cell-based therapies. However, since the effects of these treatments on cardiac function are negligible, studies on the mechanisms that regulate cardiac regeneration in mammals have accelerated. Emerging research on endogenous heart regeneration of Zebrafish (Danio rerio) is providing new insight into congenital mechanisms for complex organ regeneration. Current studies demonstrate that, mammalian neonatal hearts also have a regeneration capacity similar to Zebrafish, but this regenerative capacity is limited to the first few days after birth. Although many molecular and cellular mechanisms have been identified in this process, the Hippo signaling pathway has received the greatest attention. The activity of this pathway depends on the nuclear/cytoplasmic localization of YAP and is controlled by a number of molecular factors such as ROS, ECM and miRNAs. In the last few years studies that examining the effects of the Hippo pathway on the cardiomyocyte cell cycle have shown that components of this pathway are promising for cardiac regeneration in adults. In this review, it is aimed to give information about the Hippo pathway, which we think has an important role in reversing the damage in adult mammalian heart tissue and in the development of new therapeutic targets, and its components.

Anahtar Kelimeler

Organ regeneration, heart regeneration, hippo pathway., hippo pathway.

Kaynakça

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