Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy

Abstract MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generate...

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Autores principales:	Chen-Yun Chen, Desy S. Lee, Oi Kuan Choong, Sheng-Kai Chang, Tien Hsu, Martin W. Nicholson, Li-Wei Liu, Po-Ju Lin, Shu-Chian Ruan, Shu-Wha Lin, Chung-Yi Hu, Patrick C. H. Hsieh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4026093012a24238a07b583c66e4a5a9
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spelling	oai:doaj.org-article:4026093012a24238a07b583c66e4a5a92021-12-02T10:48:02ZCardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy10.1038/s41598-021-81700-y2045-2322https://doaj.org/article/4026093012a24238a07b583c66e4a5a92021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81700-yhttps://doaj.org/toc/2045-2322Abstract MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.Chen-Yun ChenDesy S. LeeOi Kuan ChoongSheng-Kai ChangTien HsuMartin W. NicholsonLi-Wei LiuPo-Ju LinShu-Chian RuanShu-Wha LinChung-Yi HuPatrick C. H. HsiehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen-Yun Chen Desy S. Lee Oi Kuan Choong Sheng-Kai Chang Tien Hsu Martin W. Nicholson Li-Wei Liu Po-Ju Lin Shu-Chian Ruan Shu-Wha Lin Chung-Yi Hu Patrick C. H. Hsieh Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
description	Abstract MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.
format	article
author	Chen-Yun Chen Desy S. Lee Oi Kuan Choong Sheng-Kai Chang Tien Hsu Martin W. Nicholson Li-Wei Liu Po-Ju Lin Shu-Chian Ruan Shu-Wha Lin Chung-Yi Hu Patrick C. H. Hsieh
author_facet	Chen-Yun Chen Desy S. Lee Oi Kuan Choong Sheng-Kai Chang Tien Hsu Martin W. Nicholson Li-Wei Liu Po-Ju Lin Shu-Chian Ruan Shu-Wha Lin Chung-Yi Hu Patrick C. H. Hsieh
author_sort	Chen-Yun Chen
title	Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
title_short	Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
title_full	Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
title_fullStr	Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
title_full_unstemmed	Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
title_sort	cardiac-specific microrna-125b deficiency induces perinatal death and cardiac hypertrophy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4026093012a24238a07b583c66e4a5a9
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Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy

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