Never in mitosis gene A related kinase-6 attenuates pressure overload-induced activation of the protein kinase B pathway and cardiac hypertrophy.
Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6-/-) mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC) and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt) signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Zhouyan
Z
Bian
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Haihan
H
Liao
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Yan
Y
Zhang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Qingqing
Q
Wu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China.
Heng
H
Zhou
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Zheng
Z
Yang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China.
Jinrong
J
Fu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Teng
T
Wang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China.
Ling
L
Yan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China.
Difei
D
Shen
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Hongliang
H
Li
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P. R. China; Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, P. R. China.
Qizhu
Q
Tang
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D032342:Muscle Cells / Q000187:drug effects / Q000473:pathology; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt