scholarly journals Central role of α7 nicotinic receptor in differentiation of the stratified squamous epithelium

2002 ◽  
Vol 159 (2) ◽  
pp. 325-336 ◽  
Author(s):  
Juan Arredondo ◽  
Vu Thuong Nguyen ◽  
Alexander I. Chernyavsky ◽  
Dani Bercovich ◽  
Avi Orr-Urtreger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Terminal Differentiation ◽  
Skin Barrier ◽  
Epidermal Keratinocytes ◽  
Cycle Progression ◽  
Cell Monolayers ◽  
Α7 Nachr ◽  
Keratinocyte Cell ◽  
Functional Inactivation

Several ganglionic nicotinic acetylcholine receptor (nAChR) types are abundantly expressed in nonneuronal locations, but their functions remain unknown. We found that keratinocyte α7 nAChR controls homeostasis and terminal differentiation of epidermal keratinocytes required for formation of the skin barrier. The effects of functional inactivation of α7 nAChR on keratinocyte cell cycle progression, differentiation, and apoptosis were studied in cell monolayers treated with α-bungarotoxin or antisense oligonucleotides and in the skin of Acra7 homozygous mice lacking α7 nAChR channels. Elimination of the α7 signaling pathway blocked nicotine-induced influx of 45Ca2+ and also inhibited terminal differentiation of these cells at the transcriptional and/or translational level. On the other hand, inhibition of the α7 nAChR pathway favored cell cycle progression. In the epidermis of α7−/− mice, the abnormalities in keratinocyte gene expression were associated with phenotypic changes characteristic of delayed epidermal turnover. The lack of α7 was associated with up-regulated expression of the α3 containing nAChR channels that lack α5 subunit, and both homomeric α9- and heteromeric α9α10-made nAChRs. Thus, this study demonstrates that ACh signaling through α7 nAChR channels controls late stages of keratinocyte development in the epidermis by regulating expression of the cell cycle progression, apoptosis, and terminal differentiation genes and that these effects are mediated, at least in part, by alterations in transmembrane Ca2+ influx.

scholarly journals Expression of Cyclin-Dependent Kinase Inhibitors in Epiphyseal Chondrocytes Induced to Terminally Differentiate with Thyroid Hormone

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4552-4557 ◽  
Author(s):  
R. Tracy Ballock ◽  
Xiaolan Zhou ◽  
Lynn M. Mink ◽  
Daniel H. C. Chen ◽  
Barry C. Mita ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Hormone ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Kinase Inhibitors ◽  
Terminal Differentiation ◽  
Cyclin Dependent Kinase ◽  
Growth Plate Chondrocytes ◽  
Cycle Progression ◽  
Cell Growth And Differentiation

Abstract A growing body of evidence suggests that systemic hormones and peptide growth factors may exert their effects on cell growth and differentiation in part through regulation of the cell division cycle. We hypothesized that thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through controlling cell cycle progression at the G1/S restriction point. Our results support this hypothesis by demonstrating that treatment of epiphyseal chondrocytes with thyroid hormone under chemically defined conditions results in the arrest of DNA synthesis and the onset of terminal differentiation, indicating that thyroid hormone is one factor capable of regulating the transition between cell growth and differentiation in these cells. This terminal differentiation process is associated with induction of the cyclin/cyclin-dependent kinase inhibitors p21cip-1, waf-1 and p27kip1, suggesting that thyroid hormone may regulate terminal differentiation in part by arresting cell cycle progression through induction of cyclin-dependent kinase inhibitors.

scholarly journals A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009686
Author(s):  
Akihiro Nita ◽  
Akinobu Matsumoto ◽  
Ronghao Tang ◽  
Chisa Shiraishi ◽  
Kazuya Ichihara ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wound Healing ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Skin Wound Healing ◽  
Human Epidermal Keratinocytes ◽  
Cycle Progression ◽  
Keratinocyte Proliferation

Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation–induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.

Transcription of meiotic cell cycle and terminal differentiation genes depends on a conserved chromatin associated protein, whose nuclear localisation is regulated

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5463-5473 ◽  
Author(s):  
H. White-Cooper ◽  
D. Leroy ◽  
A. MacQueen ◽  
M.T. Fuller
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Terminal Differentiation ◽  
Negative Regulator ◽  
Subcellular Localisation ◽  
Meiotic Cell ◽  
M Cell ◽  
Cycle Progression ◽  
Nuclear Localisation ◽  
Male Gametogenesis

The Drosophila always early (aly) gene coordinately regulates meiotic cell cycle progression and terminal differentiation during male gametogenesis. aly is required for transcription of key G2-M cell cycle control genes and of spermatid differentiation genes, and for maintenance of normal chromatin structure in primary spermatocytes. We show that aly encodes a homologue of the Caenorhabditis elegans gene lin-9, a negative regulator of vulval development that acts in the same SynMuvB genetic pathway as the LIN-35 Rb-like protein. The aly gene family is conserved from plants to humans. Aly protein is both cytoplasmic and nuclear in early primary spermatocytes, then resolves to a chromatin-associated pattern. It remains cytoplasmic in a loss-of-function missense allele, suggesting that nuclear localisation is critical for Aly function, and that other factors may alter Aly activity by controlling its subcellular localisation. MAPK activation occurs normally in aly mutant testes. Therefore aly, and by inference lin-9, act in parallel to, or downstream of, activation of MAPK by the RTK-Ras signalling pathway. We favour a model where aly may regulate cell cycle progression and terminal differentiation during male gametogenesis by regulating chromatin conformation in primary spermatocytes.

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