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Ultraviolet irradiation alters transforming growth factor beta/smad pathway in human skin in vivo. 2002

TaiHao Quan, and TianYuan He, and Sewon Kang, and John J Voorhees, and Gary J Fisher
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0609, USA.

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.

UI MeSH Term Description Entries
D011347 Procollagen A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains. Protocollagen,Procollagen Type M
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077293 Receptor, Transforming Growth Factor-beta Type I A transmembrane serine-threonine kinase that forms a heteromeric complex with TYPE II TGF-BETA RECEPTORS to bind TGF-BETA and regulate a variety of physiological and pathological processes including CELL CYCLE ARREST; CELL PROLIFERATION; CELL DIFFERENTIATION; WOUND HEALING; EXTRACELLULAR MATRIX production, immunosuppression and ONCOGENESIS. Activin Receptor-like Kinase 5,Receptor, TGF-beta Type I,Serine-Threonine-Protein Kinase Receptor R4,TGF-beta RPK,TGF-beta Receptor Protein Kinase,TGF-beta Type I Receptor,TGF-beta Type I Receptors,TGFBR1,TbetaR-I Kinase,Transforming Growth Factor beta Receptor I,Transforming Growth Factor, beta Receptor 1,Type I TGF-beta Receptor,Type I TGF-beta Receptors,Activin Receptor like Kinase 5,Kinase, TbetaR-I,Serine Threonine Protein Kinase Receptor R4,TGF beta Receptor Protein Kinase,TGF beta Type I Receptor,TGF beta Type I Receptors,TbetaR I Kinase,Type I TGF beta Receptor,Type I TGF beta Receptors
D000077294 Receptor, Transforming Growth Factor-beta Type II A transmembrane serine-threonine kinase that forms a heteromeric complex with TYPE I TGF-BETA RECEPTORS when bound to TGF-BETA. This receptor complex regulates a variety of physiological and pathological processes including CELL CYCLE ARREST; CELL PROLIFERATION; CELL DIFFERENTIATION; WOUND HEALING; EXTRACELLULAR MATRIX production, immunosuppression and ONCOGENESIS. TGF-beta Type II Receptor,TGF-beta Type II Receptors,TGFBR2,TbetaR-II Kinase,Transforming Growth Factor-beta Type II Receptor,Transforming Growth Factor-beta Type II Receptors,Type II TGF-beta Receptor,Type II TGF-beta Receptors,Kinase, TbetaR-II,Receptor, Transforming Growth Factor beta Type II,TGF beta Type II Receptor,TGF beta Type II Receptors,TbetaR II Kinase,Transforming Growth Factor beta Type II Receptor,Transforming Growth Factor beta Type II Receptors,Type II TGF beta Receptor,Type II TGF beta Receptors
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D014466 Ultraviolet Rays That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Actinic Rays,Black Light, Ultraviolet,UV Light,UV Radiation,Ultra-Violet Rays,Ultraviolet Light,Ultraviolet Radiation,Actinic Ray,Light, UV,Light, Ultraviolet,Radiation, UV,Radiation, Ultraviolet,Ray, Actinic,Ray, Ultra-Violet,Ray, Ultraviolet,Ultra Violet Rays,Ultra-Violet Ray,Ultraviolet Black Light,Ultraviolet Black Lights,Ultraviolet Radiations,Ultraviolet Ray

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