Epidermal keratinocytes are primarily involved in the expression of semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated the signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression is transiently increased in calcium-stimulated NHEKs, whereas it is markedly decreased in terminally differentiated NHEKs. Sema3A mRNA is mainly localized in the stratum basale and stratum suprabasale of the epidermis. We cloned the 5'-flanking region of the Sema3A gene and identified a critical region for Sema3A promoter activity within -134 base pairs of the start codon. We found transcription factor binding sites, including that for activator protein (AP)-1, in this region. Sema3A expression was increased by the co-overexpression of JunB and Fra-2 in the presence of 0.1 or 1.4 mM calcium. The calcium-mediated transient upregulation of Sema3A expression was significantly suppressed by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 or AP-1 inhibitors. These results demonstrate that the calcium-mediated transient upregulation of Sema3A in NHEKs is involved in the MEK/ERK and AP-1 signaling axis. Therefore, Sema3A mRNA may be expressed in the lower epidermis under controlled conditions by calcium via the MAPK-AP-1 axis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jid.2020.01.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of RIPK1-driven necroptosis ameliorates inflammatory hyperalgesia caused by lipopolysaccharide: involvement of TLR-, NLRP3-, and caspase-11-mediated signaling pathways.
Cell Mol Biol (Noisy-le-grand)
January 2025
Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Türkiye.
Article Synopsis
- Recent research indicates that blocking the RIPK1/RIPK3/MLKL necrosome can help reduce inflammatory pain linked to conditions like demyelination in the central nervous system.
- This study tests necrostatin-1s (Nec-1s), a specific RIPK1 inhibitor, on LPS-induced inflammatory pain in male mice, assessing pain sensitivity through hot plate tests and examining related protein changes.
- Results show that Nec-1s not only prevents LPS-induced pain relief but also reverses the activation of key proteins and signals involved in inflammation and demyelination, suggesting that RIPK1 inhibitors could be a promising treatment for managing inflammatory pain.
Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, melanoma cells must rapidly evolve to evade immune detection by simultaneously modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Angiogenesis has been implicated in this process; although an increase of vasculature initiates the immune response in normal tissue, solid tumors manage to somehow enhance blood flow while preventing immune cell infiltration.
View Article and Find Full Text PDFSuperoxide dismutase 2 deficiency in mesenchymal stromal cells induces sympathetic denervation and functional impairment of brown adipose tissue.
Pathol Int
January 2025
Department of Tumor Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Article Synopsis
- Brown adipose tissue (BAT) is critical for energy consumption, and its dysfunction can lead to metabolic diseases and obesity, especially as we age.
- The study identifies that perineurial cells, which have reduced antioxidant capacity due to lacking superoxide dismutase 2, impair BAT function by causing sympathetic nerve denervation and reducing fat oxidation.
- Targeting Meflin-expressing stromal cells may be a promising strategy to strengthen BAT function and combat age-related metabolic issues.
The role of the axonal guidance cue Semaphorin3A in innervation of the postnatal heart in health and disease.
Can J Cardiol
December 2024
Dept. of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
During cardiac development the heart is innervated by the autonomous nervous system. After development, neurons of the autonomic nervous system have limited capacity for growth and regeneration. However, in the past decades, it has become clear that cardiac nerves can regenerate after cardiac damage.
View Article and Find Full Text PDFSingle-nucleus transcriptomic profiling of the diaphragm during mechanical ventilation.
Sci Rep
December 2024
Department of Critical Care Medicine, Heping Hospital Affiliated to Changzhi Medical College, 110 South Yan'an Road, Luzhou District, Changzhi City, 046012, China.
Mechanical ventilation contributes to diaphragm atrophy and muscle weakness, which is referred to as ventilator-induced diaphragmatic dysfunction (VIDD). The pathogenesis of VIDD has not been fully understood until recently. The aim of this study was to investigate the effects of 24 h of mechanical ventilation on fibro-adipogenic progenitor (FAP) proliferation, endothelial-mesenchymal transition (EndMT), and immune cell infiltration driving diaphragm fibrosis in a rabbit model.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!