Lef‐1 controls cell cycle progression in airway basal cells to regulate proliferation and differentiation

Intestinal epithelium undergoes a rapid self-renewal process characterized by the proliferation of the crypt cells, their differentiation into mature enterocytes as they migrate up to the villi, followed by their shedding as they become senescent villus enterocytes. The exact mechanism that regulates the intestinal epithelium renewal process is not well understood, but the differential expression of regulatory genes along the crypt-villus axis may have a role. Heme oxygenase-1 (HO-1) is involved in endothelial cell cycle progression, but its role in the intestinal epithelial cell turnover has not been explored. With its effects on cell proliferation and its differential expression along the crypt-villus axis, HO-1 may play a role in the intestinal epithelial cell renewal process. In this study, we examined the role of HO-1 in the proliferation and differentiation of Caco-2 cells, a well-established in vitro model for human enterocytes. After confluence, Caco-2 cells undergo spontaneous differentiation and mimic the crypt to villus maturation observed in vivo. In preconfluent and confluent Caco-2 cells, HO-1 protein expression was determined with the immunoblot. HO-1 activity was determined by the ability of the enzyme to generate bilirubin from hemin. The effect of a HO-1 enzyme activity inhibitor, tin protoporphyrin (SnPP), on Caco-2 cell proliferation and differentiation was examined. In preconfluent cells, cell number was determined periodically as a marker of proliferation. Cell viability was measured with MTT assay. Cell differentiation was assessed by the expression of a brush border enzyme, alkaline phophatase (ALP). HO-1 was expressed in subconfluent Caco-2 cells and remained detectable until 2 days postconfluency. This timing was consistent with cells starting their differentiation and taking the features of normal intestinal epithelial cells. HO-1 was inducible in confluent Caco-2 cells by the enzyme substrate, hemin in a dose- and time-dependent manner. SnPP decreased the cell number and viability of preconfluent cells and delayed the ALP enzyme activity of confluent cells. HO-1 may be involved in intestinal cell cycle progression.

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Protein kinase C involvement in cell cycle modulation

Biochemical Society Transactions ◽

10.1042/bst20140128 ◽

2014 ◽

Vol 42 (5) ◽

pp. 1471-1476 ◽

Cited By ~ 38

Author(s):

Alessandro Poli ◽

Sara Mongiorgi ◽

Lucio Cocco ◽

Matilde Y. Follo

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Cell Models ◽

Cycle Progression ◽

Cyclin Dependent Kinases ◽

Kinase C ◽

Cell Proliferation And Differentiation ◽

Cell Cycle Modulation ◽

Proliferation And Differentiation

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.

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Function of Polyamines in Regulating Cell Cycle Progression of Cultured Silkworm Cells

Insects ◽

10.3390/insects12070624 ◽

2021 ◽

Vol 12 (7) ◽

pp. 624

Author(s):

Li Chang ◽

Zhiqing Li ◽

Hao Guo ◽

Wenchang Zhang ◽

Weiqun Lan ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Biosynthetic Pathway ◽

Expression Profiles ◽

Transcriptional Expression ◽

Cycle Progression ◽

Cell Cycle Genes ◽

Catabolic Enzymes ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation

Background: Putrescine, spermidine, and spermine are polyamines that are ubiquitously distributed in prokaryotic and eukaryotic cells, which play important roles in cell proliferation and differentiation. Methods: We investigated the expression profiles of polyamine pathway genes by qRT-PCR in different tissues of the lepidopteran silkworm. The polyamine levels in cultured silkworm cells were measured by HPLC. Spermidine and polyamine biosynthetic inhibitors were used for treating the cultured silkworm cells in order to clarify their effects on cell cycle progression. Results: We identified the anabolic and catabolic enzymes that are involved in the polyamine biosynthetic pathway in silkworm. Transcriptional expression showed at least seven genes that were expressed in different silkworm tissues. Treatments of the cultured silkworm cells with spermidine or inhibitor mixtures of DFMO and MGBG induced or inhibited the expression of cell cycle-related genes, respectively, and thus led to changed progression of the cell cycle. Conclusions: The present study is the first to identify the polyamine pathway genes and to demonstrate the roles of polyamines on cell cycle progression via regulation of the expression of cell cycle genes in silkworm.

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A mitogen gradient of dorsal midline Wnts organizes growth in the CNS

Development ◽

10.1242/dev.129.9.2087 ◽

2002 ◽

Vol 129 (9) ◽

pp. 2087-2098 ◽

Cited By ~ 41

Author(s):

Sean G. Megason ◽

Andrew P. McMahon

Keyword(s):

Cell Cycle ◽

Spinal Cord ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Dorsal Midline ◽

Proliferation And Differentiation ◽

On Line ◽

Cycle Regulation ◽

Developing Spinal Cord ◽

Correct Size

Cell cycle progression and exit must be precisely patterned during development to generate tissues of the correct size, shape and symmetry. Here we present evidence that dorsal-ventral growth of the developing spinal cord is regulated by a Wnt mitogen gradient. Wnt signaling through the β-catenin/TCF pathway positively regulates cell cycle progression and negatively regulates cell cycle exit of spinal neural precursors in part through transcriptional regulation of cyclin D1 and cyclin D2. Wnts expressed at the dorsal midline of the spinal cord, Wnt1 and Wnt3a, have mitogenic activity while more broadly expressed Wnts do not. We present several lines of evidence suggesting that dorsal midline Wnts form a dorsal to ventral concentration gradient. A growth gradient that correlates with the predicted gradient of mitogenic Wnts emerges as the neural tube grows with the proliferation rate highest dorsally and the differentiation rate highest ventrally. These data are rationalized in a ‘mitogen gradient model’ that explains how proliferation and differentiation can be patterned across a growing field of cells. Computer modeling demonstrates this model is a robust and self-regulating mechanism for patterning cell cycle regulation in a growing tissue.Supplemental data available on-line

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Kv1.3 Controls Mitochondrial Dynamics during Cell Cycle Progression

Cancers ◽

10.3390/cancers13174457 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4457

Author(s):

Jesusa Capera ◽

Mireia Pérez-Verdaguer ◽

María Navarro-Pérez ◽

Antonio Felipe

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Energy Homeostasis ◽

Mitochondrial Dynamics ◽

Mitochondrial Network ◽

Cycle Progression ◽

Genetic Ablation ◽

Obesity And Diabetes ◽

Brown Adipose ◽

Proliferation And Differentiation

The voltage-gated potassium channel Kv1.3 is a potential therapeutic target for obesity and diabetes. The genetic ablation and pharmacological inhibition of Kv1.3 lead to a lean phenotype in rodents. The mechanism of regulation of body weight and energy homeostasis involves Kv1.3 expression in different organs, including white and brown adipose tissues. Here, we show that Kv1.3 promotes the proliferation of preadipocytes through the control of mitochondrial dynamics. Kv1.3 is expressed in mitochondria exhibiting high affinity for the perinuclear population. The mitochondrial network is highly dynamic during the cell cycle, showing continuous fusion-fission events. The formation of a hyperfused mitochondrial network at the G1/S phase of the cell cycle is dependent on Kv1.3 expression. Our results demonstrate that Kv1.3 promotes preadipocyte proliferation and differentiation by controlling mitochondrial membrane potential and mitochondrial dynamics at the G1 phase of the cell cycle.

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Lef‐1 is Required for Proper Cell Cycle Progression in Airway Basal Cells

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.01752 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Chandler Walker Jensen-Cody ◽

Adrianne Crooke ◽

Thomas Lynch ◽

John Engelhardt

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Basal Cells ◽

Cycle Progression

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Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system

The Journal of Cell Biology ◽

10.1083/jcb.201004146 ◽

2011 ◽

Vol 193 (2) ◽

pp. 397-407 ◽

Cited By ~ 30

Author(s):

Céline Caillava ◽

Renaud Vandenbosch ◽

Beata Jablonska ◽

Cyrille Deboux ◽

Giulia Spigoni ◽

...

Keyword(s):

Cell Cycle ◽

Central Nervous System ◽

Nervous System ◽

Cell Cycle Progression ◽

Cyclin Dependent Kinase ◽

Cycle Progression ◽

Proliferation And Differentiation ◽

Demyelinating Lesions ◽

Underlying Mechanisms

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2−/− mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin.

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