scholarly journals A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor-like growth factor for maintaining hepatic functions in vitro and harvesting hepatocyte sheets

2016 ◽  
Vol 3 ◽  
pp. 97-106 ◽  
Author(s):  
Yoshinori Arisaka ◽  
Jun Kobayashi ◽  
Kazuo Ohashi ◽  
Kohei Tatsumi ◽  
Kyungsook Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Heparin Binding ◽  
Epidermal Growth

scholarly journals Epidermal growth factor receptor regulates pancreatic fibrosis

2009 ◽  
Vol 297 (3) ◽  
pp. G434-G441 ◽  
Author(s):  
Stacy A. Blaine ◽  
Kevin C. Ray ◽  
Kevin M. Branch ◽  
Pamela S. Robinson ◽  
Robert H. Whitehead ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Pancreatic Fibrosis ◽  
Pancreatic Stellate Cells ◽  
Heparin Binding ◽  
Epidermal Growth

The development of pancreatic fibrosis has been shown to be a major component in several diseases of the pancreas including pancreatic cancer, chronic pancreatitis, and type 2 diabetes mellitus, but its actual role in the progression of these disorders is still unknown. This fibrosis is characterized by stromal expansion and the excessive deposition of extracellular matrix (ECM) that replaces pancreatic tissue. This eventually leads to dysregulation of ECM turnover, production of cytokines, restriction of blood flow, and often exocrine and endocrine insufficiencies. Activated pancreatic stellate cells (PSCs) have been identified as key mediators in the progression of pancreatic fibrosis, serving as the predominant source of excess ECM proteins. Previously, we found that overexpression of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pancreatic islets led to intraislet fibrosis. HB-EGF binds to and activates two receptors, epidermal growth factor receptor (EGFR) and ErbB4, as well as heparin moieties and CD9/DRAP27. To understand the mechanism underlying the induction of fibrogenesis by HB-EGF, we utilized a hypomorphic allele of Egfr, the Waved-2 allele, to demonstrate that EGFR signaling regulates fibrogenesis in vivo. Using an in vitro cell migration assay, we show that HB-EGF regulates both chemoattraction and stimulation of proliferation of PSCs via EGFR activation.

scholarly journals The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF)

2002 ◽  
Vol 367 (1) ◽  
pp. 229-238 ◽  
Author(s):  
Véronique HOSPITAL ◽  
Eiichiro NISHI ◽  
Michael KLAGSBRUN ◽  
Paul COHEN ◽  
Nabil G. SEIDAH ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Active Site ◽  
Regulatory Element ◽  
Enzymic Activity ◽  
Heparin Binding ◽  
Epidermal Growth

Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met49. Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc—HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca2+, via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase.

Insulin-Induced Ectodomain Shedding of Heparin-Binding Epidermal Growth Factor-Like Growth Factor in Adipocytes In Vitro

Obesity ◽  
2010 ◽  
Vol 18 (10) ◽  
pp. 1888-1894 ◽  
Author(s):  
Takanobu Yamamoto ◽  
Takayoshi Suganami ◽  
Minako Kiso-Narita ◽  
Peggy A. Scherle ◽  
Yasutomi Kamei ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ectodomain Shedding ◽  
Heparin Binding ◽  
Epidermal Growth

scholarly journals Heparin-Binding Epidermal Growth Factor-Like Growth Factor Stimulates Androgen-Independent Prostate Tumor Growth and Antagonizes Androgen Receptor Function

Endocrinology ◽  
2002 ◽  
Vol 143 (12) ◽  
pp. 4599-4608 ◽  
Author(s):  
Rosalyn M. Adam ◽  
Jayoung Kim ◽  
Jianqing Lin ◽  
Anna Orsola ◽  
Liyan Zhuang ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Neuron Specific Enolase ◽  
Continuous Exposure ◽  
Heparin Binding ◽  
Independent State ◽  
Epidermal Growth ◽  
Androgen Independent

Abstract Peptide growth factors have been implicated in progression of prostate cancer (PCa) to the androgen-independent state; however, much of the evidence linking diffusible mitogens and survival factors to this process remains circumstantial. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a prostate stroma-derived factor, promotes survival, proliferation, and neuroendocrine differentiation of androgen-dependent LNCaP PCa cells in vitro. To test whether sustained exposure to HB-EGF can confer an androgen-independent phenotype, we generated stable populations of LNCaP cells that express constitutively a secreted form of HB-EGF (LNCaP/sHB). LNCaP/sHB cells proliferated more rapidly under androgen-depleted conditions in vitro and formed larger tumors with higher frequency in intact and castrated severe combined immunodeficient mice, in comparison to control cells. LNCaP/sHB tumors also expressed higher levels of the neuroendocrine marker, neuron-specific enolase, compared with control tumors. In castrates, increased neuron-specific enolase expression in LNCaP/sHB tumors was associated with reduced androgen receptor (AR) levels. In vitro, AR protein levels were reduced in LNCaP/sHB cells, and in transient transfection assays using an androgen-responsive promoter (mouse mammary tumor virus-long terminal repeat), LNCaP/sHB cells showed reduced sensitivity to dihydrotestosterone compared with controls. This is the first demonstration that continuous exposure of AR-positive PCa cells to a single growth factor can promote an androgen-independent phenotype in vivo. These findings also emphasize the potential role of pathways other than the AR axis in acquisition of androgen independence.

17β-Estradiol enhances heparin-binding epidermal growth factor-like growth factor production in human keratinocytes

2005 ◽  
Vol 288 (4) ◽  
pp. C813-C823 ◽  
Author(s):  
Naoko Kanda ◽  
Shinichi Watanabe
Keyword(s):  
Estrogen Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Protein ◽  
Transcriptional Activity ◽  
Human Keratinocytes ◽  
Heparin Binding ◽  
17Β Estradiol ◽  
Epidermal Growth

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) enhances reepithelialization in wounds. Estrogen is known to promote cutaneous wound repair. We examined the in vitro effects of 17β-estradiol (E2) on HB-EGF production by human keratinocytes. E2 or membrane-impermeable BSA-conjugated E2 (E2-BSA) increased HB-EGF secretion, mRNA level, and promoter activity in keratinocytes. E2 or E2-BSA enhanced in vitro wound closure in keratinocytes, and the closure was suppressed by anti-HB-EGF antibody. Activator protein-1 (AP-1) and specificity protein 1 (Sp1) sites on HB-EGF promoter were responsible for the E2- or E2-BSA-induced transactivation. Antisense oligonucleotides against c-Fos, c-Jun, and Sp1 blocked E2- or E2-BSA-induced HB-EGF transactivation. E2 or E2-BSA enhanced DNA binding and transcriptional activity of AP-1 and generated c-Fos/c-Jun heterodimers by inducing c-Fos expression. E2 or E2-BSA enhanced DNA binding and transcriptional activity of Sp1 in parallel with the enhancement of Sp1 phosphorylation. These effects of E2 or E2-BSA were not blocked by the nuclear estrogen receptor antagonist ICI-182,780 or anti-estrogen receptor-α or -β antibodies but were blocked by inhibitors of G protein, phosphatidylinositol-specific PLC, PKC-α, and MEK1. These results suggest that E2 or E2-BSA may enhance HB-EGF production via activation of AP-1 and Sp1. These effects of E2 or E2-BSA may be dependent on membrane G protein-coupled receptors different from nuclear estrogen receptors and on the receptor-mediated activities of phosphatidylinositol-specific PLC, PKC-α, and MEK1. E2 may enhance wound reepithelialization by promoting HB-EGF production in keratinocytes.

scholarly journals Expression of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Neointimal Cells Induced by Balloon Injury in Rat Carotid Arteries

1996 ◽  
Vol 16 (12) ◽  
pp. 1524-1531 ◽  
Author(s):  
Takumi Igura ◽  
Sumio Kawata ◽  
Jun-ichiro Miyagawa ◽  
Yoshiaki Inui ◽  
Shinji Tamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Carotid Arteries ◽  
Balloon Catheter ◽  
Arterial Injury ◽  
Luminal Surface ◽  
Heparin Binding ◽  
Neointimal Formation ◽  
Epidermal Growth

Balloon catheter injury of rat carotid arteries induces migration and proliferation of smooth muscle cells (SMCs), with subsequent neointimal formation. Several growth factors, such as platelet-derived growth factor and basic fibroblast growth factor, have been shown to be involved in this process, but the mechanisms that modulate the growth and/or migratory properties of SMCs remain unclear. In this study, we investigated whether heparin-binding epidermal growth factor–like growth factor (HB-EGF), which is known to be a potent SMC stimulator from in vitro study, is associated with the proliferative response of SMCs to arterial injury. Northern blot analysis showed that the transcript levels of HB-EGF increased rapidly approximately 12-fold within 2 hours after injury and declined by 2 days but remained 3-fold at 14 days. In situ hybridization analysis demonstrated that the transcript of HB-EGF remained strongly expressed in the neointima, especially near the luminal surface, at 14 days after injury. Immunohistochemical staining showed that HB-EGF protein was positive in the endothelium and only faintly visible in medial SMCs in uninjured vessels. In contrast, 2 days after injury, positive HB-EGF immunostaining was detected in the medial SMCs along the luminal surface. At 7 days, the neointimal SMCs exhibited strong immunostaining for HB-EGF, and at 14 days, they exhibited a gradient of HB-EGF expression with strong immunoreactivity in the most luminal cells. SMCs labeled with 5-bromo-2′-deoxyuridine in their nuclei showed strong immunostaining for HB-EGF protein. Furthermore, the epidermal growth factor receptor to which HB-EGF can bind was also immunostained positively in neointimal SMCs. These data suggest that HB-EGF may play an important role of the proliferation and migration of SMCs in the process of neointimal accumulation induced by arterial injury, probably in an autocrine, paracrine, and/or juxtacrine manner.

HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR IS AN AUTOCRINE MEDIATOR OF HUMAN PROSTATE STROMAL CELL GROWTH IN VITRO

2001 ◽  
Vol 165 (1) ◽  
pp. 284-288 ◽  
Author(s):  
JOSE LUIS DUQUE ◽  
ROSALYN M. ADAM ◽  
JOHN S. MULLEN ◽  
JIANQING LIN ◽  
JEROME P. RICHIE ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Epidermal Growth Factor ◽  
Stromal Cell ◽  
Human Prostate ◽  
Heparin Binding ◽  
Epidermal Growth

Localisation of stem cell factor, stanniocalcin-1, connective tissue growth factor and heparin-binding epidermal growth factor in the bovine uterus at the time of blastocyst formation

2017 ◽  
Vol 29 (11) ◽  
pp. 2127 ◽  
Author(s):  
M. Muñoz ◽  
D. Martin ◽  
S. Carrocera ◽  
M. Alonso-Guervos ◽  
M. I. Mora ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Connective Tissue ◽  
Stem Cell Factor ◽  
Tissue Growth ◽  
Heparin Binding ◽  
Epidermal Growth

Early embryonic losses before implantation account for the highest rates of reproductive failure in mammals, in particular when in vitro-produced embryos are transferred. In the present study, we used molecular biology techniques (real-time quantitative polymerase chain reaction), classical immunohistochemical staining coupled with confocal microscopy and proteomic analysis (multiple reaction monitoring and western blot analysis) to investigate the role of four growth factors in embryo–uterine interactions during blastocyst development. Supported by a validated embryo transfer model, the study investigated: (1) the expression of stem cell factor (SCF), stanniocalcin-1 (STC1), connective tissue growth factor (CTGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) in bovine uterine fluid; (2) the presence of SCF, STC1, CTGF and HB-EGF mRNA and protein in the bovine endometrium and embryos; and (3) the existence of reciprocal regulation between endometrial and embryonic expression of SCF, STC1, CTGF and HB-EGF. The results suggest that these growth factors most likely play an important role during preimplantation embryo development in cattle. The information obtained from the present study can contribute to improving the performance of in vitro culture technology in cattle and other species.

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