Pleiotropic Roles of CXCR4 in Wound Repair and Regeneration

Chen, Huating; Li, Gongchi; Liu, Y.; Ji, Shuaifei; Li, Yan; Xiang, Jiangbing; Zhou, Laixian; Gao, Huanhuan; Zhang, Wenwen; Sun, Xiaoyan; Fu, Xiaobing

doi:10.3389/fimmu.2021.668758

Cited by 23 publications

(24 citation statements)

References 97 publications

(136 reference statements)

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“…This function of the CXCR4–CXCL12 axis plays a prominent role in the recruitment of bone marrow‐derived progenitors to the uterus and endometrium 21,72,73 . It is also operative in the repair and regeneration of multiple non‐reproductive tissues after damage 74–77 …”

Section: Discussionmentioning

confidence: 99%

“…21,72,73 It is also operative in the repair and regeneration of multiple non-reproductive tissues after damage. [74][75][76][77] While CXCL12 is essential in activating inflammatory pathways that lead to PTL, CXCL12 also activates an accompanying repair mechanism; the later involves recruitment of progenitors to repair damage after infection or other insult. Proper timing of CXCR4 inhibition in the treatment of PTL may need to include reversal after control of infection, thus reactivating recruitment of progenitor cells involved in tissue repair.…”

Section: Smc-cm Induce Macrophage Function Through Cxcl12/cxcr4 Signa...mentioning

confidence: 99%

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Myometrial‐derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice

Zhang

Mamillapalli

Habata

et al. 2022

J Cellular Molecular Medi

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Preterm birth is a major contributor to neonatal mortality and morbidity. Infection results in elevation of inflammation‐related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12 levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12/CXCR4 signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine model. LPS induced CXCL12 RNA and protein levels significantly and specifically in myometrium compared with controls (3‐fold and 3.5‐fold respectively). Highest levels were found just before the start of labour. LPS also enhanced the infiltration of neutrophils, macrophages and T cells, and induced macrophage M1 polarization. In vitro studies showed that condition medium from LPS‐treated primary smooth muscle cells (SMC) induced macrophage migration, M1 polarization and upregulated inflammation‐related cytokines such as interleukin (IL)‐1, IL‐6 and tumor necrosis factor alpha (TNF‐α). AMD3100 treatment in pregnant mice led to a significant decrease in the rate of PTL (70%), prolonged pregnancy duration and suppressed macrophage infiltration into gestation tissue by 2.5‐fold. Further, in‐vitro treatment of SMC by AMD3100 suppressed the macrophage migration, decreased polarization and downregulated IL‐1, IL‐6 and TNF‐α expression. LPS treatment in pregnant mice induced PTL by increasing myometrial CXCL12, which recruits immune cells that in turn produce inflammation‐related cytokines. These effects stimulated by LPS were completely reversed by AMD3100 through blocking of CXCL12/CXCR4 signalling. Thus, the CXCL12/CXCR4 axis presents an excellent target for preventing infection and inflammation‐related PTL.

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Section: Discussionmentioning

confidence: 99%

Section: Smc-cm Induce Macrophage Function Through Cxcl12/cxcr4 Signa...mentioning

confidence: 99%

Myometrial‐derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice

Zhang

Mamillapalli

Habata

et al. 2022

J Cellular Molecular Medi

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“…Given the relevance of CXCL12 for the behavior of EPCs and SMCs as well as processes related to vascular homeostasis [ 10 , 30 , 31 ], we first evaluated the pattern of CXCL12 expression and release by EPCs and SMCs. We found that, similar to DNA damage and tissue hypoxia [ 8 , 32 ], the mechanical disruption of the SMC network increases CXCL12 release, indicating a stress-triggered induction of CXCL12 secretion.…”

Section: Discussionmentioning

confidence: 99%

Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis

Mause

Ritzel

Deck

et al. 2022

IJMS

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Endothelial progenitor cells (EPCs) are involved in vascular repair and modulate properties of smooth muscle cells (SMCs) relevant for their contribution to neointima formation following injury. Considering the relevant role of the CXCL12–CXCR4 axis in vascular homeostasis and the potential of EPCs and SMCs to release CXCL12 and express CXCR4, we analyzed the engagement of the CXCL12–CXCR4 axis in various modes of EPC–SMC interaction relevant for injury- and lipid-induced atherosclerosis. We now demonstrate that the expression and release of CXCL12 is synergistically increased in a CXCR4-dependent mechanism following EPC–SMC interaction during co-cultivation or in response to recombinant CXCL12, thus establishing an amplifying feedback loop Additionally, mechanical injury of SMCs induces increased release of CXCL12, resulting in enhanced CXCR4-dependent recruitment of EPCs to SMCs. The CXCL12–CXCR4 axis is crucially engaged in the EPC-triggered augmentation of SMC migration and the attenuation of SMC apoptosis but not in the EPC-mediated increase in SMC proliferation. Compared to EPCs alone, the alliance of EPC–SMC is superior in promoting the CXCR4-dependent proliferation and migration of endothelial cells. When direct cell–cell contact is established, EPCs protect the contractile phenotype of SMCs via CXCL12–CXCR4 and reverse cholesterol-induced transdifferentiation toward a synthetic, macrophage-like phenotype. In conclusion we show that the interaction of EPCs and SMCs unleashes a CXCL12–CXCR4-based autoregulatory feedback loop promoting regenerative processes and mediating SMC phenotype control to potentially guard vascular homeostasis.

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“…The chemotactic growth factors, cytokines, and chemokines concentration gradient, as well as the alignment of the fibrils in the ECM and provisional matrix, control the direction of fibroblast migration. Rather than crossing these fibrils, fibroblasts prefer to move along them [ 26 , 27 ]. To help them move through the matrix, fibroblasts produce proteolytic enzymes on a local level.…”

Section: The Process Of Wound Healingmentioning

confidence: 99%

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective

Trinh

Long

Anh

et al. 2022

IJMS

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Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.

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Pleiotropic Roles of CXCR4 in Wound Repair and Regeneration

Cited by 23 publications

References 97 publications

Myometrial‐derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice

Myometrial‐derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice

Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective

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