scholarly journals A microRNA program controls the transition of cardiomyocyte hyperplasia to hypertrophy and stimulates mammalian cardiac regeneration

2021 ◽  
Author(s):  
Andrea Raso ◽  
Ellen Dirkx ◽  
Vasco Sampaio-Pinto ◽  
Hamid el Azzouzi ◽  
Ryan J. Cubero ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Delivery ◽  
Cell Cycle Arrest ◽  
Regulatory Function ◽  
Viral Gene ◽  
Postnatal Life ◽  
Mouse Heart ◽  
Cell Cycle Regulators ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest

Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b∼25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b∼25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b∼25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b∼25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b∼25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart.

scholarly journals A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andrea Raso ◽  
Ellen Dirkx ◽  
Vasco Sampaio-Pinto ◽  
Hamid el Azzouzi ◽  
Ryan J. Cubero ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Delivery ◽  
Cell Cycle Arrest ◽  
Regulatory Function ◽  
Viral Gene ◽  
Postnatal Life ◽  
Mouse Heart ◽  
Cell Cycle Regulators ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest

AbstractMyocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart.

N6-Isopentenyladenosine and its Analogue N6-Benzyladenosine Induce Cell Cycle Arrest and Apoptosis in Bladder Carcinoma T24 Cells

2013 ◽  
Vol 13 (4) ◽  
pp. 672-678 ◽  
Author(s):  
Sara Castiglioni ◽  
Silvana Casati ◽  
Roberta Ottria ◽  
Pierangela Ciuffreda ◽  
Jeanette A.M. Maier
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Bladder Carcinoma ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
T24 Cells

scholarly journals Activated human CD25+B cells are able to induce cell cycle arrest and apoptosis in CD4+T‐Helper cells

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Theresa Tretter ◽  
Ram Kumar Venigalla ◽  
Volker Eckstein ◽  
Rainer Saffrich ◽  
Lorenz Hanns‐Martin
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Cell Cycle Arrest ◽  
T Helper Cells ◽  
T Helper ◽  
Induce Cell Cycle Arrest ◽  
Helper Cells ◽  
Cycle Arrest

2-MeOE2bisMATE and 2-EtE2bisMATE induce cell cycle arrest and apoptosis in breast cancer xenografts as shown by a novel ex vivo technique

2007 ◽  
Vol 111 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Paul A. Foster ◽  
Yaik T. Ho ◽  
Simon P. Newman ◽  
Philip G. Kasprzyk ◽  
Mathew P. Leese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Ex Vivo ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Breast Cancer Xenografts

scholarly journals Cell-cycle arrest in Jurkat leukaemic cells: a possible role for docosahexaenoic acid

2003 ◽  
Vol 371 (2) ◽  
pp. 621-629 ◽  
Author(s):  
Rafat A. SIDDIQUI ◽  
Laura J. JENSKI ◽  
Kevin A. HARVEY ◽  
Jacqueline D. WIESEHAN ◽  
William STILLWELL ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Docosahexaenoic Acid ◽  
Cell Cycle Arrest ◽  
Protein Phosphatase ◽  
Cyclin A ◽  
Low Doses ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Cdk2 Activity ◽  
Leukaemic Cells

Docosahexaenoic acid (DHA) is known to have anti-cancer activities by mechanisms that are not well understood. In the present study, we test one possible pathway for DHA action in Jurkat leukaemic cells. Low doses of DHA (10μM) are shown to induce cell-cycle arrest, whereas higher doses are cytotoxic. However, when cells that were pre-treated with 10μM DHA are given an additional 10μM DHA dose, cell viability rapidly decreases. Immunoblotting reveals that repeated low doses of DHA results in activation of caspase 3, implying induction of apoptosis. DHA (10μM) is shown to increase ceramide levels after 6h of incubation and, after 24h, the cells appear to be arrested in S phase. With DHA, the amount of phosphorylated retinoblastoma protein (pRb) decreases significantly. Western blot analysis also shows that DHA greatly reduces the level of cyclin A, while increasing the level of p21 WAF1, a cellular inhibitor of cyclin A/cyclin-dependent kinase 2 (cdk2) activity. Furthermore, the observed DHA-induced doubling of the ratio of hypophosphorylated pRb (hypo-pRb) to total pRb is inhibited by tautomycin and phosphatidic acid (PA), known inhibitors of protein phosphatase 1 (PP1), and by the PP2 inhibitor okadaic acid. The present study demonstrates one possible connected pathway for DHA action. By this pathway, low doses of DHA increase ceramide levels, which leads to inhibition of cdk2 activity and stimulation of PP1 and PP2A. The net effect of cdk2 inhibition and protein phosphatase activation is an inhibition of pRb phosphorylation, consequently arresting Jurkat cell growth.

Sign in / Sign up

Export Citation Format

Share Document