Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elastase degradation of elastin within alveolar walls is an important event in the development of pulmonary emphysema. In addition to elastolytic activities, elastases release growth factors from extracellular matrices and interstitial cell surfaces that can regulate elastogenesis and other cellular responses. In the present study, we demonstrate that brief treatment of matrix-laden rat pulmonary fibroblast cultures with pancreatic elastase results in the release of soluble heparin-binding epidermal growth factor-like growth factor (HB-EGF) concomitant with a decrease in HB-EGF binding to both heparan sulfate proteoglycan and receptor sites on the cells. In undigested, matrix-laden fibroblasts, HB-EGF significantly downregulates elastin mRNA via activation of epidermal growth factor receptor. Results from nuclear run-on analyses show that HB-EGF downregulates elastin mRNA via transcriptional suppression. HBEGF treatment stimulates MAP or ERK kinase (MEK)-dependent ERK1/2 phosphorylation and leads to nuclear accumulation of Fra-1. Blocking ERK1/2 activation by MEK1/2 inhibitors (PD-98059 or U-0126) diminishes HB-EGF-induced Fra-1 accumulation and subsequent downregulation of elastin mRNA. Coaddition of two elastase-released growth factors, HB-EGF and FGF-2, results in an additive inhibitory effect on elastin mRNA levels. Furthermore, HB-EGF addition to pulmonary fibroblasts increases FGF-2 mRNA and protein levels. These data suggest that HB-EGF and FGF-2 act in concert to regulate the synthesis of elastin in injury/repair situations.
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PMID:Heparin-binding EGF-like growth factor regulates elastin and FGF-2 expression in pulmonary fibroblasts. 1288 62

Chronic exposure to solar UV radiation causes marked changes in the dermal extracellular matrix that underlie the loss of resiliency and increased laxity observed in photoaged skin. In particular, the dermal elastin content increases substantially and the normal, well-organized elastic fibers are replaced by amorphous elastotic material. Transforming growth factor-beta1 (TGF-beta1) stimulates synthesis of elastin by dermal fibroblasts and may mediate the increase in elastin in chronically photodamaged skin. We investigated pathways involved in the TGF-beta1-induced increase in tropoelastin (TE), the soluble elastin monomer and assessed the role of reactive oxygen species (ROS) in the regulation of TE mRNA. Antioxidants and an inhibitor of NADPH oxidase blocked TGF-beta1-induced TE mRNA increase even when added 1.5 h after TGF-beta1, although ROS were detected for only 30 min. The TE mRNA increase required activation of Smad4, shown using Smad4 siRNA, and also involved the ERK1/2, p38 and JNK MAP kinases but not PI3K. ROS did not enhance signaling through Smad2 but did enhance activation of p38 and ERK1/2 at 10 min after TGF-beta1. These results indicate that Smad and MAPK pathways mediate TGF-beta1-induced TE expression and that ROS are required for both early signal transduction and later steps that increase elastin.
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PMID:Involvement of reactive oxygen species in TGF-beta1-induced tropoelastin expression by human dermal fibroblasts. 1970 83

Cutaneous aging is a complex and continuous biological process characterized by cellular and molecular alterations, with progressive reduction of the body's capacity to maintain the homeostasis, senescence, and/or apoptosis of the dermal cells. Fibroblast growth factors (FGF) have elicited studies to evaluate their role of repair and remodeling of the dermis during the skin anti-aging process, since they are regulatory proteins that mediate important signaling pathways and act on cell regeneration and repair processes. FGF acts primarily through binding to tyrosine kinase receptors through the autophosphorylation of their residues, promoting the phosphorylation of serine, threonine, and tyrosine residues of specific target proteins such as Raf-1, MAPK/Erk kinase, and extracellular signal-regulated kinase-1, which are part of the cascade of MAP kinases (mitogen-activated protein kinase). Then, FGF initiate signaling cascades inside the cell, where each kinase activates the following by phosphorylation, resulting in alterations of cellular functions. In addition, the FGF has a relevant role in anti-aging therapy because it is related to collagen and elastin synthesis activation responsible for skin resistance and elasticity, characteristics that are diminished with skin aging. Thus, the present article aims to review several scientific studies that demonstrated the cell signaling involved with the action of FGF on skin aging.
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PMID:Fibroblast Growth Factors: A Controlling Mechanism of Skin Aging. 3135 45