Progesterone alters human cervical epithelial and stromal cell transition and migration: Implications in cervical remodeling during pregnancy and parturition

Author(s):  
Ourlad Alzeus G. Tantengco ◽  
Lauren S. Richardson ◽  
Joy Vink ◽  
Talar Kechichian ◽  
Paul Mark B. Medina ◽  
...  
2007 ◽  
Vol 204 (3) ◽  
pp. 605-618 ◽  
Author(s):  
Jessy Deshane ◽  
Sifeng Chen ◽  
Sergio Caballero ◽  
Anna Grochot-Przeczek ◽  
Halina Was ◽  
...  

Stromal cell–derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C ζ–dependent and vascular endothelial growth factor–independent mechanism. SDF-1–induced endothelial tube formation and migration was impaired in HO-1–deficient cells. Aortic rings from HO-1−/− mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1−/− cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1–deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1–mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair.


2012 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Kerstin Schwarz ◽  
Frank Aschenbrenner ◽  
Brigitte Ruster ◽  
Manuela Kampfmann ◽  
Martina Komor ◽  
...  

Rho GTPases are involved in homing and mobilization of hematopoietic stem and progenitor cells due to their impact on cytoskeleton remodeling. We have previously shown that inhibition of Rho, Rac and Cdc42 clearly impairs adhesion of normal and leukemic hematopoietic progenitor cells (HPC) to fibronectin and migration in a three-dimensional stromal cell model. Here, we identified the Ras GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) as a target gene of Rho GTPases and analysed its role in regulating HPC motility. Overexpression of G3BP significantly enhanced adhesion of murine 32D HPC to fibronectin and human umbilical vein endothelial cells, increased the proportion of adherent cells in a flow chamber assay and promoted cell migration in a transwell assay and a three-dimensional stromal cell model suggesting a strong impact on the cytoskeleton. Immunofluorescent staining of G3BP-overexpressing fibroblasts revealed a Rho-like phenotype characterized by formation of actin stress fibers in contrast to the Rac-like phenotype of control fibroblasts. This is the first report implicating a role for G3BP in Rho GTPase-mediated signalling towards adhesion and migration of HPC. Our results may be of clinical importance, since G3BP was found overexpressed in human cancers.


2010 ◽  
Vol 138 (5) ◽  
pp. S-4
Author(s):  
Wataru Shibata ◽  
Alexander Dubeykovskiy ◽  
Michael Quante ◽  
Shigeo Takaishi ◽  
Zinaida Dubeikovskaya ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 185 ◽  
Author(s):  
Nanako Kawaguchi ◽  
Ting-Ting Zhang ◽  
Toshio Nakanishi

CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.


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