Platelet-rich plasma activates AKT signaling to promote wound healing in a mouse model of radiation-induced skin injury

Lee, Janet; Jang, Hyosun; Park, Sunhoo; Myung, Hyunwook; Kim, Kyuchang; Kim, Hyewon; Jang, Won‐Suk; Lee, Sun-Joo; Myung, Jae Kyung; Shim, Sehwan

doi:10.1186/s12967-019-2044-7

Cited by 27 publications

(22 citation statements)

References 36 publications

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“…The present study identified the AKT pathway as the main signaling pathway through which CGF exerts its immunoregulatory effects. PRP also exerts a regenerative effect via the AKT pathway [ 38 , 39 ], which supports our results. A variety of growth factors that are present in CGF extract can induce activation of AKT signaling.…”

Section: Discussionsupporting

confidence: 90%

Concentrated growth factor regulates the macrophage-mediated immune response

Liu

Zhou

et al. 2021

Regenerative Biomaterials

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Concentrated growth factor (CGF) is a promising regenerative material that serves as a scaffold and adjunct growth factor for tissue engineering. The host immune response, particularly macrophage activity, plays a critical role in injury repair and tissue regeneration. However, the biological effect of CGF on the immune response is not clear. To enrich the theoretical groundwork for clinical application, the present study examined the immunoregulatory role of CGF in macrophage functional activities in vitro. The CGF scaffold appeared as a dense fibrin network with multiple embedded leukocytes and platelets, and it was biocompatible with macrophages. Concentrated bioactive factors in the CGF extract enhanced THP-1 monocyte recruitment and promoted the maturation of suspended monocytes into adherent macrophages. CGF extract also promoted THP-1 macrophage polarization toward the M2 phenotype with upregulated CD163 expression, as detected by cell morphology and surface marker expression. A cytokine antibody array showed that CGF extract exerted a regulatory effect on macrophage functional activities by reducing secretion of the inflammatory factor interleukin (IL)-1β while inducing expression of the chemokine RANTES. Mechanistically, the AKT signaling pathway was activated, and an AKT inhibitor partially suppressed the immunomodulatory effect of CGF. Our findings reveal that CGF induces a favorable immune response mediated by macrophages, which represents a promising strategy for functional tissue regeneration.

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Section: Discussionsupporting

confidence: 90%

Concentrated growth factor regulates the macrophage-mediated immune response

Liu

Zhou

et al. 2021

Regenerative Biomaterials

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“…* P < 0:05 by a one-way ANOVA followed by Fisher's protected least post hoc test. 6 Mediators of Inflammation healing in numerous cell lines, including epithelial cells, keratinocyte, and cancer cells [23][24][25][26][27][28]. To clarify the growth-promoting mechanism of epithelial cells, the status of MAPK signaling was assessed.…”

Section: Poly P Improved the Wound Healing Of Intestinalmentioning

confidence: 99%

Probiotic-Derived Polyphosphate Accelerates Intestinal Epithelia Wound Healing through Inducing Platelet-Derived Mediators

Isozaki

Konishi

Fujiya

et al. 2021

Mediators of Inflammation

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Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), is an intractable intestinal inflammation associated with the disruption of the intestinal mucosa. We previously demonstrated that Lactobacillus brevis-derived long-chain polyphosphate (poly P) improved the intestinal barrier function by the upregulation of cell adhesion and relieved intestinal inflammation, thereby exerting a curing effect on colitis in vitro, in vivo, and in an investigator-initiated clinical study of UC. However, how poly P improves mucosal defects induced by intestinal inflammation has not been elucidated. In this study, we detected the accumulation of platelets in inflamed tissues induced by poly P in a dextran sulfate sodium- (DSS-) induced colitis mouse model. A light transmission aggregometry analysis and scanning electron microscopy showed that poly P promoted the platelet aggregation. An SRB assay and ki-67 staining showed that the supernatant of poly P-treated platelet-rich plasma (PRP) increased intestinal epithelial cell growth. A wound healing assay showed that the supernatant of poly P-treated PRP, but not poly P itself, accelerated wound healing. A Western blotting analysis indicated that mitogen-activated protein kinase activation was induced by the supernatant of poly P-treated human PRP in the epithelial cells and its wound healing effect was significantly decreased by the inhibition of ERK signaling. These data suggested that platelet-derived mediators induced by poly P improved intestinal inflammation through the promotion of epithelial cell growth by the activation of the ERK signaling pathway. The mechanism is a novel host-microbe interaction through mammalian platelet-derived mediators induced by bacterial molecules.

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“…As revealed from the results, PRP enhances cell function via AKT signaling, thereby facilitating the regeneration of irradiated skin. The ability of PRP to promote skin healing is worth conducting clinical research and application [ 69 ].…”

Section: Therapymentioning

confidence: 99%