scholarly journals Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation

Hepatology ◽  
2007 ◽  
Vol 47 (3) ◽  
pp. 996-1004 ◽  
Author(s):  
Liya Pi ◽  
Xiaodong Ding ◽  
Marda Jorgensen ◽  
Jen-Jung Pan ◽  
Seh-Hoon Oh ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Connective Tissue ◽  
Binding Site ◽  
Cell Activation ◽  
Tissue Growth ◽  
Oval Cell ◽  
Cell Adhesion And Migration ◽  
Fibronectin Binding ◽  
And Migration

scholarly journals Fibroblast Growth Factor Receptor-Mediated Rescue of x-Ephrin B1-Induced Cell Dissociation in XenopusEmbryos

2000 ◽  
Vol 20 (2) ◽  
pp. 724-734 ◽  
Author(s):  
Lisa D. Chong ◽  
Eui Kyun Park ◽  
Erin Latimer ◽  
Robert Friesel ◽  
Ira O. Daar
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Cell Adhesion And Migration ◽  
Membrane Bound ◽  
And Migration

ABSTRACT The Eph family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. Genetic evidence suggests that ephrins may transduce signals and become tyrosine phosphorylated during embryogenesis. However, the induction and functional significance of ephrin phosphorylation is not yet clear. Here, we report that when we used ectopically expressed proteins, we found that an activated fibroblast growth factor (FGF) receptor associated with and induced the phosphorylation of ephrin B1 on tyrosine. Moreover, this phosphorylation reduced the ability of overexpressed ephrin B1 to reduce cell adhesion. In addition, we identified a region in the cytoplasmic tail of ephrin B1 that is critical for interaction with the FGF receptor; we also report FGF-induced phosphorylation of ephrins in a neural tissue. This is the first demonstration of communication between the FGF receptor family and the Eph ligand family and implicates cross talk between these two cell surface molecules in regulating cell adhesion.

scholarly journals CCN2 (Connective Tissue Growth Factor) Promotes Fibroblast Adhesion to Fibronectin

2004 ◽  
Vol 15 (12) ◽  
pp. 5635-5646 ◽  
Author(s):  
Yunliang Chen ◽  
David J. Abraham ◽  
Xu Shi-wen ◽  
Jeremy D. Pearson ◽  
Carol M. Black ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Protein Kinase ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Fibroblast Adhesion

In vivo, CCN2 (connective tissue growth factor) promotes angiogenesis, osteogenesis, tissue repair, and fibrosis, through largely unknown mechanisms. In vitro, CCN2 promotes cell adhesion in a variety of systems via integrins and heparin sulfate proteoglycans (HSPGs). However, the physiological relevance of CCN2-mediated cell adhesion is unknown. Here, we find that HSPGs and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade are required for adult human dermal fibroblasts to adhere to CCN2. Endogenous CCN2 directly binds fibronectin and the fibronectin receptors integrins α4 β1 and α5 and syndecan 4. Using Ccn2-/- mouse embryonic fibroblasts, we show that loss of endogenous CCN2 results in impaired spreading on fibronectin, delayed α-smooth muscle actin stress fiber formation, and reduced ERK and focal adhesion kinase phosphorylation. These results suggest that a physiological role of CCN2 is to potentiate the ability of fibroblasts to spread on fibronectin, which may be important in modulating fibroblast adhesion to the provisional matrix during tissue development and wound healing. These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

Role of Connective Tissue Growth Factor In Endothelin-Mediated Endothelial Cell Activation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2107-2107
Author(s):  
Anna J Hernandez ◽  
Sonia Henriquez ◽  
Enrique R Maldonado ◽  
Rodeler Youte ◽  
Gregory N Prado ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Connective Tissue ◽  
Cell Activation ◽  
Fold Increase ◽  
Tissue Growth ◽  
Vegf Expression ◽  
Endothelial Cell Activation

Abstract Abstract 2107 Endothelial cell activation and elevated levels of circulating Endothelin-1 (ET-1) have been reported in patients with atherosclerosis and sickle cell disease (SCD). ET-1 is a well-described vasoconstrictor, mitogen and regulator of endothelial cells migration that has been shown to promote structural changes in blood vessels. ET-1 is produced in response to increases in vasoactive hormones, growth factors, hypoxia, shear stress and free radicals, events that are commonly observed in patients with SCD. Endothelial cell activation is in part characterized by increases of cytokines such as monocyte chemotactic protein-1 (MCP-1) and growth factors that are important in vascular maintenance and fibrogenesis such as connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). CTGF and VEGF are important for blood vessel remodeling, fibrogenesis and angiogenesis. Indeed there is evidence that incubation of smooth muscle cells with ET-1 leads to increases in CTGF and VEGF levels. However, the relationship between ET-1 and CTGF in endothelial cell activation is unclear. We hypothesize that increasing ET-1 would stimulate CTGF production and endothelial cell activation. We studied the effects of ET-1 on the human endothelial cell line, EA.hy926 (EA), as well as in primary cultures of mouse aortic endothelial cells (MAEC). We performed gene expression time course experiments (0, 2, 4, 8, 16, 24 Hr) on EA cells following incubation with 100nM ET-1 using quantitative RT-PCR with Taqman chemistries and GAPDH and beta-actin as endogenous controls. We observed increases of CTGF and VEGF expression between 4 and 8 hr for CTGF (1.74 fold increase vs time 0, n=6, P<0.03) and 4 hr for VEGF (2.14 fold increase vs time 0, n=3, P<0.04). Additional experiments on EA cells showed that incubation with 100nM ET-1 for 4 hr in the presence of BQ123 and BQ788, two inhibitors of ET-1 type A and B receptors, respectively, blocked the ET-1 stimulated rises in CTGF and VEGF as well as MCP-1 expression. We then performed western blot analyses (Abcam-CTGF antibody ab6992; Abcam VEGF antibody ab1316) and showed increases in cell associated CTGF protein levels following incubation of EA cells with 100nM ET-1 for 24 hr. The ET-1 stimulated rise in CTGF levels were significantly blunted by pre-incubation of EA cells with both BQ788 and BQ123. To study whether the effects of ET-1 were unique to EA cells, we also analyzed the effects of ET-1 on early cultures of MAEC isolated from C57BLJ mice. Consistent with our observations in human endothelial cells, incubation of MAEC with 100nM ET-1 for 4 hr were associated with increases of CTGF and VEGF expression (1.86 fold vs vehicle, n=3, P<0.03; 1.73 fold vs vehicle, n=3 P<0.04 respectively). Furthermore, ET-1 stimulated rises in CTGF and VEGF expressions were likewise blocked by pre-incubation with BQ123 andBQ788. We conclude that addition of ET-1 leads to activation of endothelial cells and increases in CTGF and VEGF from human and mouse endothelial cells. Thus we suggest that therapies designed to block ET-1 receptors will reduce endothelial cell activation in part by reducing CTGF production leading to alterations in cellular and tissue architecture. This work was supported by NIH R01HL090632 to AR and R01HL096518 to JRR. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fisp12/Mouse Connective Tissue Growth Factor Mediates Endothelial Cell Adhesion and Migration through Integrin αvβ3, Promotes Endothelial Cell Survival, and Induces Angiogenesis In Vivo

1999 ◽  
Vol 19 (4) ◽  
pp. 2958-2966 ◽  
Author(s):  
Alexander M. Babic ◽  
Chih-Chiun Chen ◽  
Lester F. Lau
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Connective Tissue ◽  
Tissue Growth ◽  
Microvascular Endothelial Cells ◽  
Endothelial Cell Survival ◽  
Vessel Growth

ABSTRACT Fisp12 was first identified as a secreted protein encoded by a growth factor-inducible immediate-early gene in mouse fibroblasts, whereas its human ortholog, CTGF (connective tissue growth factor), was identified as a mitogenic activity in conditioned media of human umbilical vein endothelial cells. Fisp12/CTGF is a member of a family of secreted proteins that includes CYR61, Nov, Elm-1, Cop-1/WISP-2, and WISP-3. Fisp12/CTGF has been shown to promote cell adhesion and mitogenesis in both fibroblasts and endothelial cells and to stimulate cell migration in fibroblasts. These findings, together with the localization of Fisp12/CTGF in angiogenic tissues, as well as in atherosclerotic plaques, suggest a possible role for Fisp12/CTGF in the regulation of vessel growth during development, wound healing, and vascular disease. In this study, we show that purified Fisp12 (mCTGF) protein promotes the adhesion of microvascular endothelial cells through the integrin receptor αvβ3. Furthermore, Fisp12 stimulates the migration of microvascular endothelial cells in culture, also through an integrin-αvβ3-dependent mechanism. In addition, the presence of Fisp12 promotes endothelial cell survival when cells are plated on laminin and deprived of growth factors, a condition that otherwise induces apoptosis. In vivo, Fisp12 induces neovascularization in rat corneal micropocket implants. These results demonstrate that Fisp12 is a novel angiogenic inducer and suggest a direct role for Fisp12 in the adhesion, migration, and survival of endothelial cells during blood vessel growth. Taken together with the recent finding that the related protein CYR61 also induces angiogenesis, we suggest that Fisp12/mCTGF and CYR61 comprise prototypes of a new family of angiogenic regulators that function, at least in part, through integrin-αvβ3-dependent pathways.

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