Abstract:
:Several proteases and their specific inhibitors modulate the interdependent processes of cell migration and matrix proteolysis as part of the global program of trauma repair. Expression of plasminogen activator inhibitor type-1 (PAI-1), a serine protease inhibitor (SERPIN) important in the control of barrier proteolysis and cell-to-matrix adhesion, for example, is spatially-temporally regulated following epithelial denudation injury in vitro as well as in vivo. PAI-1 mRNA/protein synthesis was induced early after epidermal monolayer scraping and restricted to keratinocytes comprising the motile cohort closely recapitulating, thereby, similar events during cutaneous healing. The time course of PAI-1 promoter-driven PAI-1-GFP fusion "reporter" expression in wound-juxtaposed cells approximated that of the endogenous PAI-1 gene confirming the location-specificity of gene regulation in this model. ERK activation was evident within 5 min after injury and particularly prominent in cells residing at the scrape-edge (suggesting a possible role in PAI-1 induction and/or the motile response) as was myosin light chain (MLC) phosphorylation. Indeed, MEK blockade with PD98059 or U0126 attenuated keratinocyte migration (by > or =60%), as did transient transfection of a dominant-negative ERK1 construct (40% decrease in monolayer repair), and completely inhibited PAI-1 transcript expression. Anti-sense down-regulation of PAI-1 synthesis (by 80-85%), or addition of PAI-1 neutralizing antibodies also inhibited injury site closure over a 24 h period establishing that PAI-1 was required for efficient long-term planar motility in this system. PAI-1 anti-sense transfection or actinomycin D transcriptional blockade, in contrast, did not affect the initial migratory response suggesting that residual PAI-1 protein levels (at least in transfectant cells and actinomycin D-treated cultures) may be sufficient to support early cell movement. Pharmacologic inhibition of keratinocyte MEK signaling effectively ablated scrape-induced PAI-1 mRNA expression but failed to attenuate wound-associated increases in cellular PAI-1 protein levels soon after monolayer injury. Collectively, these data suggest that basal PAI-1 transcripts may be mobilized for initial PAI-1 synthesis and, perhaps, the early motile response while maintenance of the normal rate of migration requires the prolonged PAI-1 expression that typically accompanies the repair response. To assess this possibility, scrape site closure studies were designed using keratinocytes isolated from PAI-1-/- mice. PAI-1-/- keratinocytes, in fact, had a significant wound healing defect evident even within the first 6 h following monolayer denudation injury. Addition of active PAI-1 protein to PAI-/- keratinocytes rescued the migratory phenotype that that approximating wild-type cells. These findings validate use of the present keratinocyte model to investigate injury-related controls on PAI-1 gene regulation and, collectively, implicate participation of PAI-1 in two distinct phases of epidermal wound repair.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Providence KM,Higgins PJdoi
10.1002/jcp.20016keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
297-308issue
2eissn
0021-9541issn
1097-4652journal_volume
200pub_type
杂志文章abstract::In culture, B16/C3 murine melanoma cells grown in the presence of serum undergo melanogenesis at a specific time after plating. At this time, melanin is synthesized intracellularly and then secreted into the extracellular culture fluid. We have found that melanin secretion is dependent on the presence of serum in the ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041130318
更新日期:1982-12-01 00:00:00
abstract::Thyroid hormones have a role in the regulation of hydrogen sulfide (H2 S) biosynthesis. In this study, we determined the effects of hyperthyroidism on H2 S levels in various tissues and messenger RNA (mRNA) expression of cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransfer...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28426
更新日期:2019-08-01 00:00:00
abstract::Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune respons...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.22348
更新日期:2011-02-01 00:00:00
abstract::The temperature sensitive leucyl-tRNA synthetase mutant tsHl and two revertants have been compared to the parental Chinese hamster ovary cells with respect to the effects of amino acid concentrations in the medium on growth. Elevating the leucine concentration 30- or 100-fold allowed tsHl to grow exponentially at 38.5...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040980208
更新日期:1979-02-01 00:00:00
abstract::Hyperthermia has long been known as a radio-sensitizing agent that displays anti-tumor effects, and has been developed as a therapeutic application. The mechanisms of hyperthermia-induced radio-sensitization are highly associated with inhibition of DNA repair. Our investigations aimed to show how hyperthermia inactiva...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.24302
更新日期:2013-07-01 00:00:00
abstract::This study examines the mechanism by which TGF-beta 1, an important mediator of cell growth and differentiation, blocks the differentiation of normal rat diploid fetal osteoblasts in vitro. We have established that the inability for pre-osteoblasts to differentiate is associated with changes in the expression of cell ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041600214
更新日期:1994-08-01 00:00:00
abstract::Methylxantine derivative, caffeine, is known to prevent the p53-dependent apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase, which activates p53 by phosphorylation of the Ser-15 residue. In contrast, it has been reported that caffeine induces p53-mediated apoptosis through Bax protein in n...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.10289
更新日期:2003-08-01 00:00:00
abstract::Previously we showed a rapid and transient inhibition of gap junctional communication (GJC) by platelet-derived growth factor (PDGF) in T51B rat liver epithelial cells expressing wild-type platelet-derived growth factor beta receptors (PDGFrbeta). This action of PDGF correlated with the hyperphosphorylation of the gap...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/(SICI)1097-4652(199808)176:2<332::AID-JCP1
更新日期:1998-08-01 00:00:00
abstract::Genomic imprinting in gametogenesis marks a subset of mammalian genes for parent-of-origin-dependent monoallelic expression in the offspring. Embryological and classical genetic experiments in mice that uncovered the existence of genomic imprinting nearly two decades ago produced abnormalities of growth or behavior, w...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.10129
更新日期:2002-09-01 00:00:00
abstract::We describe the isolation and characterization of a Chinese hamster ovary cell line selected for resistance to N-carbamoyloxyurea. Using the mammalian cell permeabilization assay developed in our laboratory, a detailed analysis of the target enzyme, ribonucleotide reductase (EC 1.17.4.1), was carried out. Both drug-re...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041060218
更新日期:1981-02-01 00:00:00
abstract::The anti-apoptosis protein, survivin, promotes cell survival and mitosis. Recent studies have demonstrated that survivin is expressed in normal gastric mucosa. Using an in vitro model, we examined whether survivin plays a role in the cytoprotection produced in gastric mucosa by mild irritant ethanol (ETOH) against sub...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.21358
更新日期:2008-06-01 00:00:00
abstract::This study aimed at investigating the expression and function of uracil nucleotide-sensitive receptors (P2Y(2), P2Y(4), and P2Y(6)) on osteogenic differentiation of human bone marrow stromal cells (BMSCs) in culture. Bone marrow specimens were obtained from postmenopausal female patients (68 ± 5 years old, n = 18) und...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.23014
更新日期:2012-06-01 00:00:00
abstract::Cytoplasmic poly-A containing RNA, synthesized by cultured chick embryo cells, was examined during growth in 5-bromodeoxyuridine. The kinetics of 3H-adenosine incorporation into this species of RNA, when compared to the rest of the cytoplasmic RNA, and to control cells, indicates that the rate of synthesis of this RNA...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040890103
更新日期:1976-09-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) signaling in endothelial cells is able to modulate angiogenesis and vascular remodeling, although the underlying molecular mechanisms remain poorly understood. Endoglin and ALK-1 are components of the TGF-beta receptor complex, predominantly expressed in endothelial cells, an...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.20311
更新日期:2005-08-01 00:00:00
abstract::Serum stimulation of quiescent 3T3 cells returns the cells to a proliferative state. Changes in Ca content, transport and distribution during the transition through G1 and S phase have been investigated following serum stimulation of these cells. 45 Ca exchange data indicate at least two kinetically defined cellular c...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040950110
更新日期:1978-04-01 00:00:00
abstract::Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering effects in rodent models of diabetes. The precise mechanisms whereby FGF-21 regulates metabolism remain to be determined. Here we describe the early signaling e...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.20847
更新日期:2007-01-01 00:00:00
abstract::The molecular weight of rat basic fibroblast growth factor is predicted to be 18 kDa when the amino acid sequence is read from the single AUG initiation codon found in the cDNA. DNA sequencing upstream of this AUG codon indicated, however, that there was an extended open reading frame. In vitro translation of the rat ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041480204
更新日期:1991-08-01 00:00:00
abstract::Tenascin-C, a six-armed extracellular matrix glycoprotein, is expressed in a temporally and spatially restricted pattern during carcinogenesis and invasion or metastasis of carcinoma cells in association with stromal-epithelial interactions. The human epidermoid carcinoma-derived cell lines, A431 and HEp-2, which do n...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041650104
更新日期:1995-10-01 00:00:00
abstract::A new system for studying growth of normal human mammary epithelial cells in an in vivo environment using athymic nude mice is described. Human mammary epithelial cells dissociated from reduction mammoplasty specimens were embedded within collagen gels and subsequently transplanted subcutaneously into nude mice. Histo...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041630107
更新日期:1995-04-01 00:00:00
abstract::Breast cancer (BC) is the most prevalent malignant cancer in the world, is the leading cause of cancer-related death female. Recently, there is accumulating evidence that long noncoding RNAs (lncRNAs) might as an important role in the progression of BC. (epithelial-mesenchymal transition (EMT) is considered to play a ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.28887
更新日期:2019-12-01 00:00:00
abstract::Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid h...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27857
更新日期:2019-07-01 00:00:00
abstract::Circular RNAs (circRNAs) are stable and abundantly expressed in vivo but are abnormally expressed in several diseases. This study aimed to identify circRNAs acting as potential biomarkers for cardiovascular disease (CVD). Research were retrieved from the articles published by September 2018 in eight databases to compa...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,meta分析,评审
doi:10.1002/jcp.28817
更新日期:2019-12-01 00:00:00
abstract::Oxidized-low density lipoprotein (Ox-LDL) has been shown to play an important role in impaired surfactant metabolism and transforming growth factor-β1 (TGF-β1) is a critical mediator in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). In this study, we investigated whether Ox-LDL...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.24005
更新日期:2012-09-01 00:00:00
abstract::The myelin basic protein (MBP) gene contains sequences located upstream of its transcription start site which play a key role in glial-specific transcription of the MBP promoter. Earlier analysis of the 320 bp upstream regulatory sequence of MBP has revealed multiple cis-acting regulatory motifs which differentially r...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041630213
更新日期:1995-05-01 00:00:00
abstract::Guanine nucleotides and pertussis toxin were used to test for the involvement of a guanine nucleotide binding protein in the vasopressin V1 receptor-mediated stimulation of protein kinase C activity in Swiss 3T3 cells. Addition of vasopressin in the presence of [gamma-32P]ATP and digitonin caused a marked and rapid in...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041410204
更新日期:1989-11-01 00:00:00
abstract::Epimorphin/syntaxin 2 is a high conserved and very abundant protein involved in epithelial morphogenesis in various organs. We have shown recently that epimorphin (EPM), a protein exclusively expressed on the surface of hepatic stellate cells and myofibroblasts of the liver, induces bile duct formation of hepatic stem...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.22625
更新日期:2011-11-01 00:00:00
abstract::In order to promote cell attachment, fibronectin must first undergo activation by a suitable substrate. In this study, 52 materials have been surveyed for their ability a) to bind fibronectin, b) to activate the cell-adhesive property of fibronectin, and c) to support the growth of cells. Many plastics, polysaccharide...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041090314
更新日期:1981-12-01 00:00:00
abstract::Epidermal growth factor (EGF) has been shown rapidly to inhibit the transition from G2 phase to mitosis: beyond this transition point the cells are refractory to EGF (Kinzel et al., 1990, Cancer Res., 50:7932-7936). Using synchronized HeLa cells, EGF has now been shown to induce an overall decrease of the histone H1 k...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041620107
更新日期:1995-01-01 00:00:00
abstract::Vitamin E, a dietary antioxidant, is presumed to be incorporated into the lipid bilayer of biological membranes to an extent proportional to the amount of polyunsaturated fatty acids or phospholipids in the membrane. In the present study we evaluated the distribution of incorporated polyunsaturated fatty acids (PUFA) ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041450324
更新日期:1990-12-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related death worldwide. About 1.8 million new cases were reported in 2018. Accordingly, there is an urgent need for development of effective strategies to lower the mortality and morbidity originated from this malignancy. MicroRNAs ...
journal_title:Journal of cellular physiology
pub_type: 杂志文章,评审
doi:10.1002/jcp.28872
更新日期:2019-12-01 00:00:00