Solar ultraviolet irradiation damages human skin and causes premature skin aging and skin cancer. As transforming growth factor beta plays an important role in regulating cell growth and extracellular matrix synthesis, we investigated expression of transforming growth factor beta isoforms, transforming growth factor beta receptors, and transforming growth factor beta regulated Smad transcription factors following irradiation with an ultraviolet B source and solar-simulated ultraviolet irradiation of human skin in vivo. Full-thickness, sun-protected adult human skin expressed transforming growth factor beta1, beta2, and beta3 transcripts in a ratio of 1:5:3, as determined by quantitative real-time reverse transcription polymerase chain reaction. Northern analysis demonstrated that the ultraviolet irradiation (2 minimal erythema dose) caused moderate (2-3-fold) gradual increases of transforming growth factor beta1 and beta3 mRNA expression during 3 d post exposure. In contrast, expression of transforming growth factor beta2 mRNA, the predominant form of transforming growth factor beta in human skin, decreased within 4 h after ultraviolet irradiation. In situ hybridization revealed transforming growth factor beta1, beta2, and beta3 mRNA expression in cells throughout the epidermis and the dermis in nonirradiated skin. Following ultraviolet or solar-simulated ultraviolet irradiation, transforming growth factor beta1 and beta3 mRNA were increased and transforming growth factor beta2 mRNA was reduced throughout the epidermis and dermis. No significant changes were observed in transforming growth factor beta type I receptor mRNA expression after ultraviolet irradiation. In contrast, transforming growth factor beta type II receptor mRNA expression was reduced 60% within 4 h following ultraviolet exposure in human skin in vivo. Transforming growth factor beta type II receptor mRNA levels remained reduced for 8 h and recovered by 24 h post ultraviolet. In situ hybridization revealed that ultraviolet or solar-simulated ultraviolet irradiation caused loss of transforming growth factor beta type II receptor mRNA in basal and suprabasal cells in the epidermis and dermal cells. In addition, no significant changes were observed in Smad2, Smad3, and Smad4 expression after ultraviolet irradiation. In contrast, ultraviolet and solar-simulated ultraviolet irradiation rapidly induced gene expression of Smad7, which antagonizes the actions of the transforming growth factor beta/Smad pathway. Smad7 mRNA induction occurred throughout the epidermis and dermal cells as determined by in situ hybridization. Ultraviolet irradiation also caused reduced DNA binding of Smad3/4 in human skin in vivo. Reduced Smad3/4 DNA binding was observed within 4 h following irradiation. Taken together, these results demonstrate that ultraviolet and solar-simulated ultraviolet irradiation alter the transforming growth factor beta/Smad pathway in human skin in vivo. Ultraviolet induction of Smad7 and reduction of transforming growth factor beta2 and transforming growth factor beta type II receptor should diminish transforming growth factor beta signaling, and probably contribute to the decrease of transforming growth factor beta regulated type I and type III procollagen gene expression observed in ultraviolet and solar-simulated ultraviolet irradiated human skin in vivo.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1046/j.1523-1747.2002.01834.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development and characterization of in vitro inducible immortalization of a murine microglia cell line for high throughput studies.
Sci Rep
January 2025
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, United States.
There are few in vitro models available to study microglial physiology in a homeostatic context. Recent approaches include the human induced pluripotent stem cell model, but these can be challenging for large-scale assays and may lead to batch variability. To advance our understanding of microglial biology while enabling scalability for high-throughput assays, we developed an inducible immortalized murine microglial cell line using a tetracycline expression system.
View Article and Find Full Text PDFEngineered extracellular vesicles for TGF-β encapsulation as a therapeutic strategy against LPS-induced systemic inflammation.
Int Immunopharmacol
January 2025
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address:
Inflammation underlies a wide variety of physiological and pathological processes, the Lipopolysaccharide (LPS)-induced inflammation model is widely recognized as a classical inflammatory paradigm, while Transforming growth factor-β (TGF-β) serves as a potent immunosuppressant capable of inhibiting immune responses and mitigating inflammation. However, its in vivo instability and the high cost associated with purification have imposed limitations on its clinical application. Therefore, we propose a therapeutic strategy for genetically modifying extracellular vesicles (HEVs) derived from HEK-293 T cells to incorporate TGF-β which holds potential for mitigating LPS-induced inflammation.
View Article and Find Full Text PDFBortezomib suppresses TGF-β1-mediated LOXL4 reduction through the inhibition of MEK/ERK pathways in MDA-MB-231 cells.
J Recept Signal Transduct Res
January 2025
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Lysyl oxidase (LOX), a copper-containing secretory oxidase, plays a key role in the regulation of extracellular stiffness through cross-linking with collagen and elastin. Among the LOX family of enzymes, LOX-like 4 (LOXL4) exhibits pro-tumor and anti-tumor properties; therefore, the functional role of LOXL4 in tumor progression is still under investigation. Here, we first determined that transforming growth factor-β1 (TGF-β1) significantly decreased LOXL4 expression in human breast cancer MDA-MB-231 cells, which suggested that decreased LOXL4 may participate in tumor progression.
View Article and Find Full Text PDFExploring Azithromycin's Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation.
Pharmaceuticals (Basel)
January 2025
Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi Arabia.
Background: Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, and psychological impairments, triggering oxidative stress, neuroinflammation, and neurodegeneration. This study examined the neuroprotective effects of azithromycin (AZI) in TBI.
Methods: TBI was induced in rats using the weight-drop method.
Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical Stretch-Induced Lung Injury.
Int J Mol Sci
January 2025
Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anesthesia, Genera Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria.
Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial cells from healthy donor lung tissue with the catalytic domain of telomerase and the SV40 large T/small t-antigen. These cells exhibited satisfactory growth characteristics and largely maintained their native characteristics, including morphology, cell surface marker expression, angiogenic potential and the protein composition of secreted extracellular vesicles.
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!