Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy
Lysosomal-associated protein transmembrane 5 (LAPTM5) is mainly expressed in immune cells and has been reported to regulate inflammation, apoptosis and autophagy. Although LAPTM5 is expressed in the heart, whether LAPTM5 plays a role in regulating cardiac function remains unknown. Here, we show that...
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doaj-d72904591000437e91840299184ee1992021-10-06T04:45:43ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-10-01810.3389/fcvm.2021.740526740526Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac HypertrophyLu Gao0Sen Guo1Rui Long2Lili Xiao3Rui Yao4Xiaolin Zheng5Yanzhou Zhang6Xiaofang Wang7Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaLysosomal-associated protein transmembrane 5 (LAPTM5) is mainly expressed in immune cells and has been reported to regulate inflammation, apoptosis and autophagy. Although LAPTM5 is expressed in the heart, whether LAPTM5 plays a role in regulating cardiac function remains unknown. Here, we show that the expression of LAPTM5 is dramatically decreased in murine hypertrophic hearts and isolated hypertrophic cardiomyocytes. In this study, we investigated the role of LAPTM5 in pathological cardiac hypertrophy and its possible mechanism. Our results show that LAPTM5 gene deletion significantly exacerbates cardiac remodeling, which can be demonstrated by reduced myocardial hypertrophy, fibrosis, ventricular dilation and preserved ejection function, whereas the opposite phenotype was observed in LAPTM5 overexpression mice. In line with the in vivo results, knockdown of LAPTM5 exaggerated angiotensin II-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes, whereas overexpression of LAPTM5 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, LAPTM5 directly bound to Rac1 and further inhibited MEK-ERK1/2 signaling, which ultimately regulated the development of cardiac hypertrophy. In addition, the antihypertrophic effect of LAPTM5 was largely blocked by constitutively active mutant Rac1 (G12V). In conclusion, our results suggest that LAPTM5 is involved in pathological cardiac hypertrophy and that targeting LAPTM5 has great therapeutic potential in the treatment of pathological cardiac hypertrophy.https://www.frontiersin.org/articles/10.3389/fcvm.2021.740526/fullLAPTM5cardiac hypertrophysignal transductionRac1MEK-ERK pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lu Gao Sen Guo Rui Long Lili Xiao Rui Yao Xiaolin Zheng Yanzhou Zhang Xiaofang Wang |
spellingShingle |
Lu Gao Sen Guo Rui Long Lili Xiao Rui Yao Xiaolin Zheng Yanzhou Zhang Xiaofang Wang Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy Frontiers in Cardiovascular Medicine LAPTM5 cardiac hypertrophy signal transduction Rac1 MEK-ERK pathway |
author_facet |
Lu Gao Sen Guo Rui Long Lili Xiao Rui Yao Xiaolin Zheng Yanzhou Zhang Xiaofang Wang |
author_sort |
Lu Gao |
title |
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy |
title_short |
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy |
title_full |
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy |
title_fullStr |
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy |
title_full_unstemmed |
Lysosomal-Associated Protein Transmembrane 5 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy |
title_sort |
lysosomal-associated protein transmembrane 5 functions as a novel negative regulator of pathological cardiac hypertrophy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2021-10-01 |
description |
Lysosomal-associated protein transmembrane 5 (LAPTM5) is mainly expressed in immune cells and has been reported to regulate inflammation, apoptosis and autophagy. Although LAPTM5 is expressed in the heart, whether LAPTM5 plays a role in regulating cardiac function remains unknown. Here, we show that the expression of LAPTM5 is dramatically decreased in murine hypertrophic hearts and isolated hypertrophic cardiomyocytes. In this study, we investigated the role of LAPTM5 in pathological cardiac hypertrophy and its possible mechanism. Our results show that LAPTM5 gene deletion significantly exacerbates cardiac remodeling, which can be demonstrated by reduced myocardial hypertrophy, fibrosis, ventricular dilation and preserved ejection function, whereas the opposite phenotype was observed in LAPTM5 overexpression mice. In line with the in vivo results, knockdown of LAPTM5 exaggerated angiotensin II-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes, whereas overexpression of LAPTM5 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, LAPTM5 directly bound to Rac1 and further inhibited MEK-ERK1/2 signaling, which ultimately regulated the development of cardiac hypertrophy. In addition, the antihypertrophic effect of LAPTM5 was largely blocked by constitutively active mutant Rac1 (G12V). In conclusion, our results suggest that LAPTM5 is involved in pathological cardiac hypertrophy and that targeting LAPTM5 has great therapeutic potential in the treatment of pathological cardiac hypertrophy. |
topic |
LAPTM5 cardiac hypertrophy signal transduction Rac1 MEK-ERK pathway |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2021.740526/full |
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