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
Kaynakça
- 1. Benjamin E., Muntner P., Alonso A., Bittencourt M., Callaway C., Carson A et al. American Heart Association Council on, C. Prevention Statistics, S. Stroke Statistics, Heart disease and stroke statistics-2019 update: areport from the American Heart Association, Circulation 139 (10) (2019)e56–e528.
- 2. Vujic A., Natarajan N., Lee R. Molecular Mechanisms of Heart Regeneration. Seminars in Cells and Developmental Biology. 2020;100:20-28.
- 3. Borne S., Diez J., Blankesteijn W., Verjans J., Hofstra L., Narula J. Myocardial Remodeling After Infarction: The Role of Myofibroblasts, Nature Review Cardiology.2010;7(1):30–37.
- 4. Laflamme M., Murry C. Heart Regeneration. Nature. 2011;473(7347):326–335.
- 5. Whelan R., Kaplinskiy V., Kitsis R. Cell Death in the Pathogenesis of Heart Disease: Mechanisms and Significance, Annual Review of Physiology. 2010;72:19–44.
- 6. Niederberger P., Farine E., Raillard M., Dornbierer M., Freed D. H., Large S. R et al. Heart Transplantation With Donation After Circulatory Death. Circulation Heart failure. 2019;12(4).
- 7. Porello E., Mahmoud A., Simpson E., Hill J., Richardson J., Olson E., Sadek H. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011; 331(6020):1078-80.
- 8. Romanes G. J. (1972). Cunningham’s Textbook of Anatomy. 17th Edition. Oxford University Press. London.
- 9. Poon K. L., Brand T. The Zebrafish Model System in Cardiovascular Research: A Tiny Fish with Mighty Prospects. Global Cardiology Science & Practice. 2013;4: 10-28.
- 10. Arman S. Pestisit Kaynaklı Kardiyak Toksisite Araştırmalarında Zebra Balığı (Danio rerio). Düzce Üniversitesi Bilim ve Teknoloji Dergisi. 2019;7: 1417-1430.
- 11. Porrello E. R., Mahmoud A. I., Simpson E., Hill J. A., Richardson J. A., Olson E. N et al. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011;331(6020):1078-80.
- 12. Porrello E.R., Olson E.N. A Neonatal Blueprint for Cardiac Regeneration. Stem Cell Research. 2014;13(3):556-70.
- 13. Ziheng M., Jacob J., Hung S., Wang J. The Hippo Pathway in Cardiac Regeneration and Homeostasis: New Perspectives for Cell Free Therapy in The Injured Heart. Biomolecules. 2020;10(7):1024.
- 14. Cardoso A., Pereira A., Sadek H. Mechanism of Neonatal Heart Regeneration. Current Cardiology Reports. 2020;22(5):33.
- 15. Pan D. The Hippo Signaling Pathway in Development and Cancer. Developmental Cell. 2010;19(4):491-505.
- 16. Zhao B., Tumaneng K., Guan K.L., The Hippo Pathway in Organ Size Control, Tissue Regeneration and Stem Cell-Renewal. Nature Cell Biology. 2011;13(8):877-83.
- 17. Wang J., Liu S., Heallen T., Martin J.F. The Hippo Pathway in the Heart: Pivotal Roles in Development, Disease and Regeneration. Nature Reviews Cardiology. 2018;15(11):672-684.
- 18. Heallen T., Morikawa Y., Leach J., Tao G., Willerson J.T., Johnson R.L., Martin J.F. Hippo Signaling Impedes Adult Heart Regeneration. Devolepment. 2013;140(23):4683-90.
- 19. Piccolo S., Dupont S., Cordenonsi M. The Biology of YAP/TAZ: Hippo Signaling and Beyond. Physiological Reviews. 2014;94(4):1287-312
- 20. Puento B.N., Kimura W., Muralidhar S.A., Moon J., Amatruda J.F., Phelps K.L et.al. The Oxygen-rich Postnatal Environment Induces Cardiomyocyte Cell-cycle Arrest Through DNA Damage Response. Cell. 2014;157:565-79.
- 21. Fisher D.J., Heymann M.A., Rudolph A.M. Myocardial Oxygen and Carbonhydrate Consumption in Fetal Lambs in Utero and in Adult Sheep. The American Journal of Physology. 1980;238:399-405.
- 22. Lopaschuk G.D., Collins-Nakai R.L., Itoi T. Developmental Changes in Energy Substrate use by the Heart. Cardiovascular Research. 1992;26:1172-80.
- 23. Wisneski J.A., Gertz E.W., Neese R.A.,Gruenke L.D., Morris D.L., Craig J.C. Metabolic Fate of Extracted Glucose in Normal Human Myocardium. The Journal of Clinical Investigation. 1985;76:1819-27.
- 24. Pang J., Phua Q., Soh B. Applications of miRNAs in Cardiac Development, Disease Progression and Regeneration Stem Cell Research and Therapy. 2019;10(1):336.
- 25. Tian Y., Liu Y., Wang T., Zhou N., Kong J., Chen L et.al. A MicroRNA -Hippo Pathway that Promotes Cardiomyocyte Proliferation and Cardiac Regeneration in Mice. Science Translational Medicine. 2015;7(279):279ra38.
- 26. Bassat E., Mutlak Y., Genzelinakh A., Shadrin I., Umansky K., Yifa O. The Extracellular Matrix Protein Agrin Promotes Heart Regeneration in Mice. Nature. 2017;547(7662):179-184.
- 27. Notari M., Rubio A., Guaus S., Jorba I., Mulero L., Navajas D. The Local Microenvironment Limits the Regenerative Potential of the Mouse Neonatal Heart. Science. 2018;4(5):eaao5553.
- 28. Porello E., Mahmoud A., Simpson E., Hill J., Richardson J., Olson E. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011;331(6020):1078-80.
- 29. Ramjee V., Li D., Manderfield L., Liu F.,Engleka K., Aghajanian H. Epicardial YAP/TAZ Orchestrate an Immunosuppressive Response Following Myocardial Infarction. American Society for Clinical Investigation. 2017;127(3):899-911.
- 30. Singh A., Ramesh S., Cibi M., Yun L., Li J., Li L. Hippo Signaling Mediators Yap and Taz are Required in the Epicardium for Coronary Vasculature Development. Cell Reports. 2016;15(7):1384-1393.
- 31. Leach J., Heallen T., Zhang M., Rahmani M., Morikawa Y., Tepesi M. Hippo Pathway Deficiency Reverses Systolic Heart Failure After Infarction. Nature. 2017; 550(7675):260-264.
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
- 1. Benjamin E., Muntner P., Alonso A., Bittencourt M., Callaway C., Carson A et al. American Heart Association Council on, C. Prevention Statistics, S. Stroke Statistics, Heart disease and stroke statistics-2019 update: areport from the American Heart Association, Circulation 139 (10) (2019)e56–e528.
- 2. Vujic A., Natarajan N., Lee R. Molecular Mechanisms of Heart Regeneration. Seminars in Cells and Developmental Biology. 2020;100:20-28.
- 3. Borne S., Diez J., Blankesteijn W., Verjans J., Hofstra L., Narula J. Myocardial Remodeling After Infarction: The Role of Myofibroblasts, Nature Review Cardiology.2010;7(1):30–37.
- 4. Laflamme M., Murry C. Heart Regeneration. Nature. 2011;473(7347):326–335.
- 5. Whelan R., Kaplinskiy V., Kitsis R. Cell Death in the Pathogenesis of Heart Disease: Mechanisms and Significance, Annual Review of Physiology. 2010;72:19–44.
- 6. Niederberger P., Farine E., Raillard M., Dornbierer M., Freed D. H., Large S. R et al. Heart Transplantation With Donation After Circulatory Death. Circulation Heart failure. 2019;12(4).
- 7. Porello E., Mahmoud A., Simpson E., Hill J., Richardson J., Olson E., Sadek H. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011; 331(6020):1078-80.
- 8. Romanes G. J. (1972). Cunningham’s Textbook of Anatomy. 17th Edition. Oxford University Press. London.
- 9. Poon K. L., Brand T. The Zebrafish Model System in Cardiovascular Research: A Tiny Fish with Mighty Prospects. Global Cardiology Science & Practice. 2013;4: 10-28.
- 10. Arman S. Pestisit Kaynaklı Kardiyak Toksisite Araştırmalarında Zebra Balığı (Danio rerio). Düzce Üniversitesi Bilim ve Teknoloji Dergisi. 2019;7: 1417-1430.
- 11. Porrello E. R., Mahmoud A. I., Simpson E., Hill J. A., Richardson J. A., Olson E. N et al. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011;331(6020):1078-80.
- 12. Porrello E.R., Olson E.N. A Neonatal Blueprint for Cardiac Regeneration. Stem Cell Research. 2014;13(3):556-70.
- 13. Ziheng M., Jacob J., Hung S., Wang J. The Hippo Pathway in Cardiac Regeneration and Homeostasis: New Perspectives for Cell Free Therapy in The Injured Heart. Biomolecules. 2020;10(7):1024.
- 14. Cardoso A., Pereira A., Sadek H. Mechanism of Neonatal Heart Regeneration. Current Cardiology Reports. 2020;22(5):33.
- 15. Pan D. The Hippo Signaling Pathway in Development and Cancer. Developmental Cell. 2010;19(4):491-505.
- 16. Zhao B., Tumaneng K., Guan K.L., The Hippo Pathway in Organ Size Control, Tissue Regeneration and Stem Cell-Renewal. Nature Cell Biology. 2011;13(8):877-83.
- 17. Wang J., Liu S., Heallen T., Martin J.F. The Hippo Pathway in the Heart: Pivotal Roles in Development, Disease and Regeneration. Nature Reviews Cardiology. 2018;15(11):672-684.
- 18. Heallen T., Morikawa Y., Leach J., Tao G., Willerson J.T., Johnson R.L., Martin J.F. Hippo Signaling Impedes Adult Heart Regeneration. Devolepment. 2013;140(23):4683-90.
- 19. Piccolo S., Dupont S., Cordenonsi M. The Biology of YAP/TAZ: Hippo Signaling and Beyond. Physiological Reviews. 2014;94(4):1287-312
- 20. Puento B.N., Kimura W., Muralidhar S.A., Moon J., Amatruda J.F., Phelps K.L et.al. The Oxygen-rich Postnatal Environment Induces Cardiomyocyte Cell-cycle Arrest Through DNA Damage Response. Cell. 2014;157:565-79.
- 21. Fisher D.J., Heymann M.A., Rudolph A.M. Myocardial Oxygen and Carbonhydrate Consumption in Fetal Lambs in Utero and in Adult Sheep. The American Journal of Physology. 1980;238:399-405.
- 22. Lopaschuk G.D., Collins-Nakai R.L., Itoi T. Developmental Changes in Energy Substrate use by the Heart. Cardiovascular Research. 1992;26:1172-80.
- 23. Wisneski J.A., Gertz E.W., Neese R.A.,Gruenke L.D., Morris D.L., Craig J.C. Metabolic Fate of Extracted Glucose in Normal Human Myocardium. The Journal of Clinical Investigation. 1985;76:1819-27.
- 24. Pang J., Phua Q., Soh B. Applications of miRNAs in Cardiac Development, Disease Progression and Regeneration Stem Cell Research and Therapy. 2019;10(1):336.
- 25. Tian Y., Liu Y., Wang T., Zhou N., Kong J., Chen L et.al. A MicroRNA -Hippo Pathway that Promotes Cardiomyocyte Proliferation and Cardiac Regeneration in Mice. Science Translational Medicine. 2015;7(279):279ra38.
- 26. Bassat E., Mutlak Y., Genzelinakh A., Shadrin I., Umansky K., Yifa O. The Extracellular Matrix Protein Agrin Promotes Heart Regeneration in Mice. Nature. 2017;547(7662):179-184.
- 27. Notari M., Rubio A., Guaus S., Jorba I., Mulero L., Navajas D. The Local Microenvironment Limits the Regenerative Potential of the Mouse Neonatal Heart. Science. 2018;4(5):eaao5553.
- 28. Porello E., Mahmoud A., Simpson E., Hill J., Richardson J., Olson E. Transient Regenerative Potential of the Neonatal Mouse Heart. Science. 2011;331(6020):1078-80.
- 29. Ramjee V., Li D., Manderfield L., Liu F.,Engleka K., Aghajanian H. Epicardial YAP/TAZ Orchestrate an Immunosuppressive Response Following Myocardial Infarction. American Society for Clinical Investigation. 2017;127(3):899-911.
- 30. Singh A., Ramesh S., Cibi M., Yun L., Li J., Li L. Hippo Signaling Mediators Yap and Taz are Required in the Epicardium for Coronary Vasculature Development. Cell Reports. 2016;15(7):1384-1393.
- 31. Leach J., Heallen T., Zhang M., Rahmani M., Morikawa Y., Tepesi M. Hippo Pathway Deficiency Reverses Systolic Heart Failure After Infarction. Nature. 2017; 550(7675):260-264.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Derleme |
| Yazarlar | |
| Yayımlanma Tarihi | 31 Mart 2022 |
| Kabul Tarihi | 11 Ocak 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 31 Sayı: 1 |
