Stromal Cell-derived Factor 1/CXCR4 Signaling, Stem and Fractures

2013 ◽  
pp. 200-213
Author(s):  
Hiromu Ito
2009 ◽  
Vol 60 (3) ◽  
pp. 813-823 ◽  
Author(s):  
Toshiyuki Kitaori ◽  
Hiromu Ito ◽  
Edward M. Schwarz ◽  
Ryosuke Tsutsumi ◽  
Hiroyuki Yoshitomi ◽  
...  

2004 ◽  
Vol 76 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Hui Peng ◽  
Yunlong Huang ◽  
Jeremy Rose ◽  
David Erichsen ◽  
Shelley Herek ◽  
...  

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 546-554 ◽  
Author(s):  
Carmen Hernández-López ◽  
Alberto Varas ◽  
Rosa Sacedón ◽  
Eva Jiménez ◽  
Juan José Muñoz ◽  
...  

Abstract The present study investigated the potential role of stromal cell–derived factor 1 (SDF-1) in human intrathymic T-cell differentiation. Results show that SDF-1 is produced by human thymic epithelial cells from the subcapsular and medullary areas, and its receptor, CXCR4, is up-regulated on CD34+ precursor cells committed to the T-cell lineage. Chimeric human-mouse fetal thymus organ culture (FTOC) seeded with purified CD34+thymic progenitors and treated with neutralizing antibodies against SDF-1 or CXCR4 showed a significant reduction of the number of human thymocytes and an arrested thymocyte differentiation in the transition between CD34+ precursor cells and CD4+ immature thymocytes. SDF-1–treated FTOC showed an increase of human thymocyte numbers, mainly affecting the most immature subpopulations. Moreover, these results suggest that CXCR4/SDF-1 signaling is not critical for the CD34+ cell precursor recruitment to the thymus. On the other hand, SDF-1 significantly increased the viability of CD34+ T-cell precursors modulating the expression ofBCL-2 and BAX genes, and stimulated the proliferation of CD34+ thymic precursor cells, particularly in synergy with interleukin 7 (IL-7), but not with other cytokines, such as stem cell factor or flt3-ligand. Accordingly, only IL-7 was able to up-regulate CXCR4 expression on CD34+ thymic progenitors. In addition, deprivation of SDF-1 partially inhibited human thymocyte expansion induced by IL-7 in human-mouse FTOC. This study indicates that SDF-1/CXCR4 signaling is required for the survival, expansion, and subsequent differentiation of human early thymocytes and identifies a new mechanism by which IL-7 mediates its effects on human thymopoiesis.


JCI Insight ◽  
2018 ◽  
Vol 3 (23) ◽  
Author(s):  
Keisuke Omori ◽  
Nanae Nagata ◽  
Kaori Kurata ◽  
Yoko Fukushima ◽  
Erika Sekihachi ◽  
...  

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Yun-Ling Li ◽  
Yu-Fen Li ◽  
Hua-Feng Li ◽  
Huai-Qing Lv ◽  
De-Zhong Sun

The present study aims to explore the role of stromal cell-derived factor-1α (SDF-1α)/stromal cell-derived factor receptor-4 (CXCR4) signaling pathway to the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2009 to December 2010, 102 patients with NPC and 80 patients with chronic nasopharyngitis were enrolled for the study. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting were employed to determine the expressions of SDF-1α and CXCR4 proteins in NPC tissues and chronic nasopharyngitis tissues. Chi-square test was conducted to analyze the associations of the expressions of SDF-1α and CXCR4 proteins with the clinicopathological features of NPC patients. Spearman rank correlation analysis was used to analyze the correlation between the SDF-1α protein expression and CXCR4 protein expression. The mRNA and protein expressions of SDF-1α and CXCR4 in NPC tissues were significantly higher than those in chronic nasopharyngitis tissues. The expressions of SDF-1α and CXCR4 proteins showed associations with T staging, N staging, tumor node metastasis (TNM) staging, skull base invasion, and cervical lymph node metastasis of NPC patients. Compared with NPC patients showing negative expressions of SDF-1α and CXCR4 proteins, those with positive expressions of SDF-1α and CXCR4 proteins had a significantly shorter survival time. SDF-1α protein, CXCR4 protein, EBV-IgG status, T staging, N staging, TNM staging, skull base invasion, and cervical lymph node metastasis were independent risk factors for the prognosis of NPC. The findings indicated that SDF-1α/CXCR4 signaling pathway might be associated with the clinicopathological features and prognosis of patients with NPC.


2003 ◽  
Vol 290 (2) ◽  
pp. 289-302 ◽  
Author(s):  
Daisuke Uchida ◽  
Nasima-Mila Begum ◽  
Ammar Almofti ◽  
Koh-ichi Nakashiro ◽  
Hitoshi Kawamata ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Wasana Sumanasekera ◽  
Shujing Dai ◽  
Piero Anversa ◽  
Roberto Bolli ◽  
Gregg Rokosh

Stromal cell derived factor-1 α (SDF1) through the interaction with it receptor CXCR4 plays an important role in regulating the localization and function of hematopoietic stem cells. Recently, we have described SDF1-CXCR4 signaling in the heart and found it to regulate myocardial survival through the activation of ERK and AKT. CXCR4 is known to couple to the heterotrimeric G-Protein, Gi. The G-protein receptor kinase 6 (GRK6), may serve to uncouple the receptor from downstream signaling or to facilitate signaling via phosphorylation- dependent and independent mechanisms. To further understand cardiac SDF1-CXCR4 signaling and function we used rat clonal cKit + cardiac stem cells (rCSC) to assess the role of GRK6 in CXCR4 responses to SDF1. To specifically target GRK6 actions in SDF1-CXCR4 signaling and function in rCSCs we used siRNA to knockdown GRK6 in vitro. In untreated rCSCs, GRK6 specific siRNA significantly knocked down the expression of GRK6 by 50 – 60% which lead to significant decreases in levels of P-AKT, and P-ERK (about 70 - 90% respectively, P± 0.05) and increased levels of P-JNK, P-p38, and Caveolin1 in untreated rCSC. The treatment of rCSC with 25 nM SDF1 significantly increased GRK6 expression and this increase was attenuated by GRK6 specific siRNA. AKT, ERK, JNK, and p38 phosphorylation were significantly increased 5 min after rCSC treatment with 25nM SDF1 (0.5–3 fold increase, P<0.05) and GRK6 siRNA significantly attenuated SDF1activation (0.5 to 2 fold decrease, P<0.05). Our results indicate that in rCSC, GRK6 is necessary for SDF1-CXCR4 dependent ERK and AKT signaling Thus in rCSCs GRK6 serves predominantly in G-protein independent SDF1-CXCR4 signaling possibly through caveolar signaling complexes. In conclusion, in rCSCs SDF1-CXCR4 interaction activates downstream ERK and AKT activation via a GRK6 dependent mechanism. These findings will be important for the understanding of SDF1-CXCR4 regulation of rCSC function.


2021 ◽  
Vol 12 ◽  
Author(s):  
Huating Chen ◽  
Gongchi Li ◽  
Yiqiong Liu ◽  
Shuaifei Ji ◽  
Yan Li ◽  
...  

Wound healing is a multi-step process that includes multiple cellular events such as cell proliferation, cell adhesion, and chemotactic response as well as cell apoptosis. Accumulating studies have documented the significance of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) signaling in wound repair and regeneration. However, the molecular mechanism of regeneration is not clear. This review describes various types of tissue regeneration that CXCR4 participates in and how the efficiency of regeneration is increased by CXCR4 overexpression. It emphasizes the pleiotropic effects of CXCR4 in regeneration. By delving into the specific molecular mechanisms of CXCR4, we hope to provide a theoretical basis for tissue engineering and future regenerative medicine.


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