Role of Pim-1 in Smooth Muscle Cell Proliferation

Katakami, Naoto; Kaneto, Hideaki; Hao, Hiroyuki; Umayahara, Yutaka; Fujitani, Yoshio; Sakamoto, Kenya; Gorogawa, Shin-ichi; Yasuda, Tetsuyuki; Kawamori, Dan; Kajimoto, Yoshitaka; Matsuhisa, Munehide; Yutani, Chikao; Hori, Masatsugu; Yamasaki, Yoshimitsu

doi:10.1074/jbc.m409140200

Cited by 65 publications

(53 citation statements)

References 28 publications

(21 reference statements)

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“…The function of Pim kinases in proliferation is also clearly shown by the compound Pim knockout mice, which show much reduced body size at birth and throughout postnatal life (6). It was reported that, in smooth muscle cells, infection of adenovirus encoding KD Pim-1 remarkably reduced cell growth (53). Pim-1 was also found to be highly expressed in prostate cancer cells, and overexpression of Pim-1 kinase dramatically enhances the growth of tumor cells (54).…”

Section: Discussionmentioning

confidence: 91%

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Zhang

Wang

Magnuson

2007

Molecular Cancer Research

113

103

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Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle. In the present study, site-directed mutagenesis and phosphorylated-specific antibodies were used as tools to identify the sites phosphorylated by Pim-1 and the consequences of this phosphorylation. What , it localizes primarily in the cytoplasm and the effect of phosphorylation on stability is minimal. Cotransfection of wild-type Pim-1 with p21 increases the rate of proliferation compared with cotransfection of p21 with kinase-dead Pim-1. Knocking down Pim-1 expression greatly decreases the rate of proliferation of H1299 cells and their ability to grow in soft agar. These data suggest that Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 and by promoting cell proliferation. (Mol Cancer Res 2007;5(9):909 -22)

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Section: Discussionmentioning

confidence: 91%

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Zhang

Wang

Magnuson

2007

Molecular Cancer Research

113

103

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“…These data demonstrate the ability of Pim-1 to preserve the endogenous regenerative potential of CPCs in spite of persistent hyperglycemia. Furthermore, Pim-1 is necessary for vascular smooth muscle proliferation, 28 and CPCs engineered with Pim-1 have been shown to promote neovascularization in a mouse infarct model. 27 The present data showing the expression of hPIM-1 in vascular smooth muscle cells provide a key for interpretation of the preserved arteriole density in hPIM-1-transduced diabetic hearts.…”

Section: Katare Et Almentioning

confidence: 99%

Intravenous Gene Therapy With PIM-1 Via a Cardiotropic Viral Vector Halts the Progression of Diabetic Cardiomyopathy Through Promotion of Prosurvival Signaling

Katare

Caporali

Zentilin

et al. 2011

Circulation Research

122

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Rationale: Studies in transgenic mice showed the key role of (Pim-1) (proviral integration site for Moloney murine leukemia virus-1) in the control of cardiomyocyte function and viability.Objective: We investigated whether Pim-1 represents a novel mechanistic target for the cure of diabetic cardiomyopathy, a steadily increasing cause of nonischemic heart failure. Methods and Results:In streptozotocin-induced type 1 diabetic mice, Pim-1 protein levels declined during progression of cardiomyopathy, along with upregulation of Pim-1 inhibitors, protein phosphatase 2A, and microRNA-1. Moreover, diabetic hearts showed low levels of antiapoptotic B-cell lymphoma-2 (Bcl-2) protein and increased proapoptotic caspase-3 activity. Studies on adult rat cardiomyocytes and murine cardiac progenitor cells challenged with high glucose confirmed the in vivo expressional changes. In rescue studies, anti-microRNA-1 boosted Pim-1 and Bcl-2 expression and promoted cardiomyocyte and cardiac progenitor cell survival under high glucose conditions. Similarly, transfection with Pim-1 plasmid prevented high glucoseinduced cardiomyocyte and cardiac progenitor cell apoptosis. Finally, a single intravenous injection of human PIM-1 via cardiotropic serotype-9 adeno-associated virus (1؋10 10 or 5؋10 10 genome copies per animal) at 4 weeks after diabetes induction led to sustained cardiac overexpression of Pim-1 and improved diastolic function and prevented left ventricular dilation and failure. Histological examination showed reduced cardiomyocyte apoptosis and fibrosis in association with increased c-kit ؉ cells and cardiomyocyte proliferation, whereas molecular analysis confirmed activation of the prosurvival pathway and conservation of sarcoendoplasmic reticulum Ca 2؉-ATPase and ␣-myosin heavy chain in Pim-1-treated hearts. Key Words: diabetic cardiomyopathies Ⅲ diastolic dysfunction Ⅲ Pim-1 kinase Ⅲ gene therapy Ⅲ cardiac stem cells A common form of cardiomyopathy directly related to diabetes mellitus (DM), ie, diabetic cardiomyopathy, typically progresses from diastolic dysfunction to heart failure in the absence of coronary artery disease or hypertension. [1][2][3] Studies in animal models illustrate the complexity of the underpinning pathogenic mechanisms (reviewed in Bugger and Abel 4 ). Hence, a deeper understanding of targets for early therapeutic interventions is critically needed. Conclusions:Recent work from Muraski and colleagues 5 uncovered the pivotal role of (Pim-1) (proviral integration site for Moloney murine leukemia virus-1), a member of the serine/threonine protein kinase family, in the cardiac cell response to stressors. Promotion of cardiomyocyte survival by Pim-1 is mediated by activation of B-cell lymphoma-2 (Bcl-2), phosphorylation/ inhibition of Bcl-2-associated death promoter (Bad), and maintenance of mitochondrial integrity. 6,7 By inducing c-Myc, nucleostemin, and cyclin E expression and p21 phosphorylation, Pim-1 increases the proliferative activity of cardiac progenitor cells (CPCs). 8,9 Furthermore, Pim-1 acts...

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“…Genes like the Txk kinase and c-myb that are most commonly associated with thymocyte differentiation (40-42) may perhaps also act to facilitate T cell survival in the responding lymph nodes and spleen (42)(43)(44). Additional evidence for active transcriptional pathways in the splenic CD8 ϩ D b NP 366 ϩ set that could contribute to T cell survival comes from the identification of genes like pim1, which interacts with c-myb (45) and can enhance c-myb transcriptional activity (46). Analysis using this ''broad-brush'' array approach has thus provided the important insight that, although effector T cells operating in a site of pathology have a more activated phenotype, there is a concomitant narrowing in the spectrum of gene expression that may perhaps be associated with diminished survival in the longer term.…”

Section: Discussionmentioning

confidence: 99%

Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

Marshall

Olivas

Andreansky

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The restriction of influenza A virus replication to mouse respiratory epithelium means that this host response is anatomically compartmentalized, on the one hand, to sites of T cell stimulation and proliferation in the secondary lymphoid tissue and, on the other hand, to the site of effector T cell function and pathology in the pneumonic lung. Thus, it is hardly surprising that virus-specific CD8 ؉ T cells recovered by bronchoalveolar lavage (BAL) from the infected respiratory tract seem more ''activated'' in terms of both cytolytic activity and cytokine production than those cells isolated from the spleen. The present analysis uses Affymetrix microarray technology to compare profiles of gene expression in these two lineage-related, yet anatomically separate, lymphocyte populations. Ninety differentially expressed genes were identified for influenza-specific CD8 ؉ D b NP 366 ؉ T cells obtained directly ex vivo by BAL or spleen disruption, with nine genes being further analyzed by quantitative, real-time PCR at the population level. Integrin ␣E, for example, was shown by Affymetrix and real-time mRNA analyses and then by single-cell PCR and protein staining to be present at a much higher prevalence on the BAL CD8 ؉ D b NP366 ؉ set. The unpredicted finding, however, was that mRNA expression for 75% of the 90 genes was lower in T cells from the BAL than from the spleen. Apparently, the localization of virus-specific CD8 ؉ T cells to the site of virus-induced pathology is associated with a narrowing, or ''focusing,'' of gene expression that favors enhanced effector function in the damaged, ''high-antigen load'' environment of the pneumonic lung.Affymetrix gene array ͉ cytotoxic T cell ͉ influenza A virus ͉ viral immunology

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Role of Pim-1 in Smooth Muscle Cell Proliferation

Cited by 65 publications

References 28 publications

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Intravenous Gene Therapy With PIM-1 Via a Cardiotropic Viral Vector Halts the Progression of Diabetic Cardiomyopathy Through Promotion of Prosurvival Signaling

Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

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Role of Pim-1 in Smooth Muscle Cell Proliferation

Cited by 65 publications

References 28 publications

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Intravenous Gene Therapy With PIM-1 Via a Cardiotropic Viral Vector Halts the Progression of Diabetic Cardiomyopathy Through Promotion of Prosurvival Signaling

Effector CD8+T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

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Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression