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Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy

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Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy. / Kluge, Annika; Rangrez, Ashraf Yusuf; Kilian, Lucia Sophie; Pott, Jost; Bernt, Alexander; Frauen, Robert; Rohrbeck, Astrid; Frey, Norbert; Frank, Derk.

In: J MOL CELL CARDIOL, Vol. 129, 04.2019, p. 130-143.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kluge, A, Rangrez, AY, Kilian, LS, Pott, J, Bernt, A, Frauen, R, Rohrbeck, A, Frey, N & Frank, D 2019, 'Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy', J MOL CELL CARDIOL, vol. 129, pp. 130-143. https://doi.org/10.1016/j.yjmcc.2019.01.028

APA

Kluge, A., Rangrez, A. Y., Kilian, L. S., Pott, J., Bernt, A., Frauen, R., Rohrbeck, A., Frey, N., & Frank, D. (2019). Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy. J MOL CELL CARDIOL, 129, 130-143. https://doi.org/10.1016/j.yjmcc.2019.01.028

Vancouver

Kluge A, Rangrez AY, Kilian LS, Pott J, Bernt A, Frauen R et al. Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy. J MOL CELL CARDIOL. 2019 Apr;129:130-143. https://doi.org/10.1016/j.yjmcc.2019.01.028

Bibtex

@article{1727a263d21046368e54bdcf979f2864,
title = "Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy",
abstract = "Cardiac remodeling is induced by mechanical or humoral stress causing pathological changes to the heart. Here, we aimed at identifying the role of differentially regulated genes upon dynamic mechanical stretch. Microarray of dynamic stretch induced neonatal rat ventricular cardiomyocytes (NRVCMs) discovered Rho family GTPase 1 (Rnd1) as one of the significantly upregulated genes, a cardiac role of which is not known yet. Rnd1 was consistently upregulated in NRVCMs after dynamic stretch or phenylephrine (PE) stimulation, and in a mouse model of pressure overload. Overexpression of Rnd1 in NRVCMs activated the fetal gene program (including nppa and nppb) effected into a significant increase in cell surface area in untreated, stretched or PE-treated cells. Furthermore, Rnd1 overexpression showed a positive effect on cell proliferation as detected by significant increase in Ki67, Phosphohistone H3, and EdU positive NRVCMs. Through a Yeast two-hybrid screen and immunoprecipitation analysis, we identified Myozap, an intercalated disc protein, as novel interaction partner of Rnd1. Importantly, functional analysis of this interaction revealed the importance of RND1 in the RhoA and Myozap protein network that activates serum-response factor (SRF) signaling. In summary, we identified Rnd1 as a novel stretch-sensitive gene which influences cell proliferation and cellular hypertrophy via activation of RhoA-mediated SRF dependent and independent signaling pathways.",
keywords = "Animals, Animals, Newborn, Biomechanical Phenomena, Cardiomegaly/metabolism, Cell Cycle, Cell Proliferation, Intracellular Signaling Peptides and Proteins/metabolism, Models, Biological, Myocytes, Cardiac/metabolism, Protein Binding, Rats, Wistar, Serum Response Factor/metabolism, Signal Transduction, Stress, Physiological, rho GTP-Binding Proteins/metabolism, rhoA GTP-Binding Protein/metabolism",
author = "Annika Kluge and Rangrez, {Ashraf Yusuf} and Kilian, {Lucia Sophie} and Jost Pott and Alexander Bernt and Robert Frauen and Astrid Rohrbeck and Norbert Frey and Derk Frank",
note = "Copyright {\textcopyright} 2019. Published by Elsevier Ltd.",
year = "2019",
month = apr,
doi = "10.1016/j.yjmcc.2019.01.028",
language = "English",
volume = "129",
pages = "130--143",
journal = "J MOL CELL CARDIOL",
issn = "0022-2828",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy

AU - Kluge, Annika

AU - Rangrez, Ashraf Yusuf

AU - Kilian, Lucia Sophie

AU - Pott, Jost

AU - Bernt, Alexander

AU - Frauen, Robert

AU - Rohrbeck, Astrid

AU - Frey, Norbert

AU - Frank, Derk

N1 - Copyright © 2019. Published by Elsevier Ltd.

PY - 2019/4

Y1 - 2019/4

N2 - Cardiac remodeling is induced by mechanical or humoral stress causing pathological changes to the heart. Here, we aimed at identifying the role of differentially regulated genes upon dynamic mechanical stretch. Microarray of dynamic stretch induced neonatal rat ventricular cardiomyocytes (NRVCMs) discovered Rho family GTPase 1 (Rnd1) as one of the significantly upregulated genes, a cardiac role of which is not known yet. Rnd1 was consistently upregulated in NRVCMs after dynamic stretch or phenylephrine (PE) stimulation, and in a mouse model of pressure overload. Overexpression of Rnd1 in NRVCMs activated the fetal gene program (including nppa and nppb) effected into a significant increase in cell surface area in untreated, stretched or PE-treated cells. Furthermore, Rnd1 overexpression showed a positive effect on cell proliferation as detected by significant increase in Ki67, Phosphohistone H3, and EdU positive NRVCMs. Through a Yeast two-hybrid screen and immunoprecipitation analysis, we identified Myozap, an intercalated disc protein, as novel interaction partner of Rnd1. Importantly, functional analysis of this interaction revealed the importance of RND1 in the RhoA and Myozap protein network that activates serum-response factor (SRF) signaling. In summary, we identified Rnd1 as a novel stretch-sensitive gene which influences cell proliferation and cellular hypertrophy via activation of RhoA-mediated SRF dependent and independent signaling pathways.

AB - Cardiac remodeling is induced by mechanical or humoral stress causing pathological changes to the heart. Here, we aimed at identifying the role of differentially regulated genes upon dynamic mechanical stretch. Microarray of dynamic stretch induced neonatal rat ventricular cardiomyocytes (NRVCMs) discovered Rho family GTPase 1 (Rnd1) as one of the significantly upregulated genes, a cardiac role of which is not known yet. Rnd1 was consistently upregulated in NRVCMs after dynamic stretch or phenylephrine (PE) stimulation, and in a mouse model of pressure overload. Overexpression of Rnd1 in NRVCMs activated the fetal gene program (including nppa and nppb) effected into a significant increase in cell surface area in untreated, stretched or PE-treated cells. Furthermore, Rnd1 overexpression showed a positive effect on cell proliferation as detected by significant increase in Ki67, Phosphohistone H3, and EdU positive NRVCMs. Through a Yeast two-hybrid screen and immunoprecipitation analysis, we identified Myozap, an intercalated disc protein, as novel interaction partner of Rnd1. Importantly, functional analysis of this interaction revealed the importance of RND1 in the RhoA and Myozap protein network that activates serum-response factor (SRF) signaling. In summary, we identified Rnd1 as a novel stretch-sensitive gene which influences cell proliferation and cellular hypertrophy via activation of RhoA-mediated SRF dependent and independent signaling pathways.

KW - Animals

KW - Animals, Newborn

KW - Biomechanical Phenomena

KW - Cardiomegaly/metabolism

KW - Cell Cycle

KW - Cell Proliferation

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Models, Biological

KW - Myocytes, Cardiac/metabolism

KW - Protein Binding

KW - Rats, Wistar

KW - Serum Response Factor/metabolism

KW - Signal Transduction

KW - Stress, Physiological

KW - rho GTP-Binding Proteins/metabolism

KW - rhoA GTP-Binding Protein/metabolism

U2 - 10.1016/j.yjmcc.2019.01.028

DO - 10.1016/j.yjmcc.2019.01.028

M3 - SCORING: Journal article

C2 - 30797814

VL - 129

SP - 130

EP - 143

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

ER -