DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence

Elmansi, Ahmed M.; Eisa, Nada H.; Periyasamy‐Thandavan, Sudharsan; Kondrikova, Galina; Kondrikov, Dmitry; Calkins, Maggie M.; Aguilar-Pérez, Alexandra; Chen, Jie; Johnson, Maribeth H.; Shi, Xingming; Reitman, Charles A.; McGee‐Lawrence, Meghan E.; Crawford, Kyler; Dwinell, Michael B.; Volkman, Brian F.; Blumer, Joe B.; Luttrell, Louis M.; McCorvy, John D.; Hill, William

doi:10.1021/acsptsci.2c00040

Cited by 3 publications

(1 citation statement)

References 73 publications

(150 reference statements)

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“…These inflammatory cells produce various cytokines (23). In combination with TGFβ1, these cytokines induce the migration of fibroblasts, epithelial cells, and endothelial cells (24)(25)(26)(27). Thrombin and factors of the fibrinolytic system increase vascular permeability (28,29).…”

Section: Discussionmentioning

confidence: 99%

The EGF Motif With CXDXXXXYXCXC Sequence Suppresses Fibrosis in a Mouse Skin Wound Model

Kitano

Ishikawa

Masaoka

et al. 2023

In Vivo

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Background/Aim: Fibrosis is an essential process for wound healing, but excessive fibrosis, such as keloids and hypertrophic scars, can cause cosmetic and functional problems. These lesions are caused by abnormal deposition and shrinkage of collagen fibers. The light chain of FIX, a plasma protein essential for hemostasis, has the amino acid sequence CXDXXXXYXCXC in the EGF domain. Peptides containing this sequence inhibited stromal growth in a mouse transplant tumor model. In this study, the effect of the FIX light chain on wound healing was studied. Materials and Methods: A full-layer wound was made on the back of each mouse, and cDNA encoding the light chain of mouse FIX (F9-LC) in an expression vector was injected locally once each week using a non-viral vector. Histochemical analysis of the wound was then performed to assess the effects on wound healing. Moreover, the effect of F9-LC on fibroblasts was studied in vitro. Results: Macroscopic observation showed that wounds with forced expression of F9-LC appeared flatter and had fewer wrinkles than control wounds. Tissue collagen staining and immunostaining revealed that administration of F9-LC suppressed collagen 1 and 3 deposition and decreased α-smooth muscle actin expression. Electron microscopy revealed sparse and disorganized collagen fibers in the F9-LC-treated mice. In experiments using fibroblasts, addition of a recombinant protein of the FIX light chain disrupted the typical spindle shape and alignment of fibroblasts. Conclusion: F9-LC is a new candidate for use in treatments to regulate excessive fibrosis and contraction in wound healing.

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Section: Discussionmentioning

confidence: 99%

The EGF Motif With CXDXXXXYXCXC Sequence Suppresses Fibrosis in a Mouse Skin Wound Model

Kitano

Ishikawa

Masaoka

et al. 2023

In Vivo

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Mechanistic study of the effect of flexible fixation and load‐bearing stress environment on fracture healing and shaping

Li,

Deng,

2024

Anim Models and Exp Med

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BackgroundThe biomechanical environment created by suture‐button fixation Latarjet is conducive to the healing and shaping of the transplanted coracoid, but its mechanism remains unclear. The latest research has found that the absence of stem cell chemokine (CXCL12) impeded bone regeneration in Sonic Hedgehog (SHH)‐deficient animals. However, whether the biomechanical environment affects SHH and CXCL12 function has not been studied.MethodsRat fracture models were constructed to simulate stress environments under non‐load‐bearing and load‐bearing conditions. The fracture healing and shaping, as well as the expression levels of SHH and CXCL12, were assessed through gross viewing, micro‐computed tomography (micro‐CT), and histochemical staining.ResultsUnder flexible fixation, the relative bone volume (BV/TV) of rats exposed to the load‐bearing stress environment was significantly higher than that of rats under a non‐load‐bearing stress environment (p ≤ 0.05). Adverse bone shaping was not observed in rats subjected to flexible fixation. The levels of SHH and CXCL12 in load‐bearing rats exhibited significant elevation (p ≤ 0.05). Under a load‐bearing stress environment, no significant difference was observed in the BV/TV between the flexible fixation group and the rigid fixation group (p ≥ 0.05), but there was excessive hyperplasia of the fracture callus in the rigid fixation group. The levels of SHH and CXCL12 in rats subjected to rigid fixation were significantly elevated (p ≤ 0.05).ConclusionsFlexible fixation and load‐bearing stress environment may contribute to bone healing and shaping by influencing the levels of SHH and CXCL12, suggested that this mechanism may be relevant to the healing and shaping of the transplanted coracoid after suture‐button fixation Latarjet.

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A consensus single-cell transcriptomic atlas of dermal fibroblast heterogeneity

Ascensión,

Izeta

2024

Preprint

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Single-cell RNA sequencing (scRNAseq) studies have unveiled large transcriptomic heterogeneity within both human and mouse dermal fibroblasts, but a consensus atlas that spans both species is lacking. Here, by studying 25 human and 9 mouse datasets through a semi-supervised procedure, we categorize 15 distinct human fibroblast populations across 5 main axes. Analysis of human fibroblast markers characteristic of each population suggested diverse functions, such as position-dependent ECM synthesis, association with immune responses or structural roles in skin appendages. Similarly, mouse fibroblasts were categorized into 17 populations across 5 axes. Comparison of mouse and human fibroblast populations highlighted similarities suggesting a degree of functional overlap, though nuanced differences were also noted: transcriptomically, human axes seem to segregate by function, while mouse axes seem to prioritize positional information over function. Importantly, addition of newer datasets did not significantly change the defined population structure. This study enhances our understanding of dermal fibroblast diversity, shedding light on species-specific distinctions as well as shared functionalities.

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DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence

Cited by 3 publications

References 73 publications

The EGF Motif With CXDXXXXYXCXC Sequence Suppresses Fibrosis in a Mouse Skin Wound Model

The EGF Motif With CXDXXXXYXCXC Sequence Suppresses Fibrosis in a Mouse Skin Wound Model

Mechanistic study of the effect of flexible fixation and load‐bearing stress environment on fracture healing and shaping

A consensus single-cell transcriptomic atlas of dermal fibroblast heterogeneity

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