scholarly journals Stromal-Cell Deletion of STAT3 Protects Mice from Kidney Fibrosis by Inhibiting Pericytes Trans-Differentiation and Migration

2021 ◽  
Author(s):  
Amrendra K. Ajay ◽  
Li Zhao ◽  
Shruti Vig ◽  
Mai Fujikawa ◽  
Sudhir Thakurela ◽  
...  
Keyword(s):  
Stromal Cell ◽  
Kidney Fibrosis ◽  
And Migration ◽  
Cell Deletion

scholarly journals Stromal-cell deletion of STAT3 protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration

2021 ◽  
Author(s):  
Amrendra K Ajay ◽  
Li Zhao ◽  
Shruti Vig ◽  
Mai Fujiwara ◽  
Sudhir Thakurela ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Kidney Fibrosis ◽  
Knock Out ◽  
Exact Function ◽  
And Migration

Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although tubular Stat3 deletion in tubular epithelial cells is known to protect mice from kidney fibrosis, the exact function of STAT3 in stromal cells remains unknown. We utilized stromal-cell Stat3 knock-out (KO) mice, CRISPR and pharmacologic activators and inhibitors of STAT3 to investigate its function in pericyte-like cells. STAT3 is phosphorylated in tubular epithelial cells in acute kidney injury whereas its activation expanded to interstitial cells in chronic kidney disease in mice and humans. Stromal cell-specific deletion of Stat3 protects mice from folic acid- and aristolochic acid-induced kidney fibrosis. Mechanistically, STAT3 directly regulates the inflammatory pathway, differentiation of pericytes into myofibroblasts. Specifically, STAT3 activation leads to an increase in migration and profibrotic signaling in genome-edited pericyte-like cells, 10T1/2. Conversely, Stat3 KO or blocking STAT3 function inhibits detachment, spreading, migration, and profibrotic signaling. Furthermore, STAT3 binds to Collagen1a1 promoter of fibrotic mouse kidneys and in pericyte-like cells. Together, our study identifies a previously unknown function of STAT3 in stromal cells that promotes kidney fibrosis and may have therapeutic value in fibrotic kidney disease.

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

2021 ◽  
pp. 111276
Author(s):  
Ourlad Alzeus G. Tantengco ◽  
Lauren S. Richardson ◽  
Joy Vink ◽  
Talar Kechichian ◽  
Paul Mark B. Medina ◽  
...  
Keyword(s):  
Stromal Cell ◽  
Cervical Remodeling ◽  
And Migration ◽  
Cell Transition

scholarly journals SAT-107 BONE MARROW STROMAL CELL ANTIGEN-1 MEDIATES ACUTE KIDNEY INJURY AND KIDNEY FIBROSIS

2019 ◽  
Vol 4 (7) ◽  
pp. S50-S51
Author(s):  
T. INOUE ◽  
J. Yao ◽  
L. Huang ◽  
D. Rosin ◽  
K. Ishihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Stromal Cell ◽  
Bone Marrow Stromal Cell ◽  
Kidney Injury ◽  
Kidney Fibrosis ◽  
Marrow Stromal Cell ◽  
Cell Antigen

scholarly journals Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanism

2007 ◽  
Vol 204 (3) ◽  
pp. 605-618 ◽  
Author(s):  
Jessy Deshane ◽  
Sifeng Chen ◽  
Sergio Caballero ◽  
Anna Grochot-Przeczek ◽  
Halina Was ◽  
...  
Keyword(s):  
Wound Healing ◽  
Heme Oxygenase ◽  
Stromal Cell ◽  
Tube Formation ◽  
Heme Oxygenase 1 ◽  
Impaired Wound Healing ◽  
Endothelial Tube Formation ◽  
Stromal Cell Derived Factor ◽  
And Migration

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.

scholarly journals Novel Role of Ras-GTPase Activating Protein SH3 Domain-Binding Protein G3BP in Adhesion and Migration of 32D Myeloid Progenitor Cells

2012 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Kerstin Schwarz ◽  
Frank Aschenbrenner ◽  
Brigitte Ruster ◽  
Manuela Kampfmann ◽  
Martina Komor ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Rho Gtpases ◽  
Stromal Cell ◽  
Cell Model ◽  
Binding Protein ◽  
Three Dimensional ◽  
Sh3 Domain ◽  
Gtpase Activating Protein ◽  
Ras Gtpase ◽  
And Migration

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.

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