10 Kazu Kikuchi – Regulation of Cardiomyocyte Cell Cycle (Proliferation and Maturation)

Kazu Kikuchi, PhD

Director of the Department of Cardiac Regeneration Biology at the National Cerebral and Cardiovascular Center, Japan

Dr. Kazu Kikuchi is the Director of the Department of Cardiac Regeneration Biology at the National Cerebral and Cardiovascular Center in Japan.  Prior to this position, Dr. Kazu Kikuchi was the head of the Cardiac Regeneration Laboratory at the Victor Chang Cardiac Research Institute. Dr. Kikuchi earned both his undergraduate and graduate (PhD) degrees  from the Tohoku University School of Medicine in Japan and then completed a post-doctoral fellowship in Motonari Kondo’s Lab at Duke University in North Carolina, USA.  Throughout his career, Dr. Kikuchi has studied organ regeneration, more specifically heart regeneration.  

Despite his current academic successes, Dr. Kikuchi has admitted that he did poorly at school as a child, as he spent a lot of time fishing for crayfish and catching beetles with friends, he rather enjoyed spending time in nature, but through hard work and determination, he graduated at the top of his class. (Timms, 2018).

Certainly Dr. Kikuchi’s fascination with fish has shaped his career, as he grew intrigued by the capabilities of some freshwater fish to repair their heart, spinal column, kidneys, and fins. Dr. Kikuchi found that although zebrafish are 70% genetically identical to humans, zebrafish have significant differences including their remarkable abilities in regenerating tissues without scarring, possibly due to the activities of their immune system cells – specifically T cells. More recently Dr. Kikuchi and his lab have been identifying and investigating the enzymes and transcription factors that are involved in zebrafish heart repair.  Specifically, they have found that the ventricular injury stimulates increased production of the enzyme Raldh2/AldhIa2 (within epicardial and endocardial cells close to the site of injury), which is necessary for cardiomyocyte proliferation (Kikuchi, 2012).  Additionally, they have found that after injury to the heart, there is an increased production of transcription factor klf1 within proliferating cardiomyoctes.

Klf1 appears to play two roles:

1) enhancing cardiomyocyte proliferation (by up-regulating cell proliferation gene expression)

2) stimulating cardiomyocte de-differentiation (by repressing myocardial differentiation) and influencing mitochondrial metabolism

It’s important to note that within this study, the team was interested to find out whether klf1 does appear to have a role during fetal heart development or not. They expected it to be influential during this time of cardiomyocyte proliferation and maturation (Ogawa et.al, 2021).

References:

– History of major discoveries – victor chang cardiac research institute. The Victor Chang Cardiac Research Institute. (n.d.). https://www.victorchang.edu.au/heart-research/major-discoveries

– Timms, J. (2018, June 2). Fishing for clues – dr Kazu Kikuchi – Victor Chang cardiac research institute. The Victor Chang Cardiac Research Institute. https://www.victorchang.edu.au/news/fishing-for-clues

– Timms, J. (Ed.). (2021, April 9). New discovery: Heart attack – victor chang cardiac research institute. The Victor Chang Cardiac Research Institute. https://www.victorchang.edu.au/news/discovery-uncovers-switch-revolutionise-heart-attack-treatment

– Kikuchi, K., Holdway, J. E., Major, R. J., Blum, N., Dahn, R. D., Begemann, G., & Poss, K. D. (2011). Retinoic acid production by endocardium and Epicardium is an injury response essential for zebrafish heart regeneration. Developmental Cell, 20(3), 397–404. https://doi.org/10.1016/j.devcel.2011.01.010

– Kikuchi, K., & Poss, K. D. (2012). Cardiac regenerative capacity and Mechanisms. Annual Review of Cell and Developmental Biology, 28(1), 719–741. https://doi.org/10.1146/annurev-cellbio-101011-155739