Akt promotes increased cardiomyocyte cycling and expansion of the cardiac progenitor cell population.
Activation of Akt is associated with enhanced cell cycling and cellular proliferation in nonmyocytes, but this effect of nuclear Akt accumulation has not been explored in the context of the myocardium. Cardiac-specific expression of nuclear-targeted Akt (Akt/nuc) in transgenics prolongs postnatal cell cycling as evidenced by increased numbers of Ki67+ cardiomyocytes at 2 to 3 weeks after birth. Similarly, nuclear-targeting of Akt promotes expansion of the presumptive cardiac progenitor cell population as assessed by immunolabeling for c-kit in combination with myocyte-specific markers Nkx 2.5 or MEF 2C. Increases in pro-proliferative cytokines, including tumor-necrosis superfamily 8, interleukin-17e, and hepatocyte growth factor, were found in nuclear-targeted Akt myocardial samples. Concurrent signaling mediated by paracrine factors downstream of Akt/nuc expression may be responsible for phenotypic effects of nuclear-targeted Akt in the myocardium, including enhanced cell proliferation and expansion of the stem cell population.
Gude
Natalie
N
San Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
Muraski
John
J
Rubio
Marta
M
Kajstura
Jan
J
Schaefer
Erik
E
Anversa
Piero
P
Sussman
Mark A
MA
D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D032342:Muscle Cells / Q000166:cytology / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt