Human keratinocyte-derived microvesicle miRNA-21 promotes skin wound healing in diabetic rats through facilitating fibroblast function and angiogenesis

Li, Qian; Zhao, Hui; Chen, Weimin; Huang, Ping; Bi, Jianping

doi:10.1016/j.biocel.2019.105570

Cited by 79 publications

(77 citation statements)

References 49 publications

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“…The capillaries supply oxygen and nutrients to the fibrocytes and epithelial cells, whereas the dermal layer protects the corium layer from bacteria and radiation [13]. These three cell types communicate and interact with one another via paracrine actions [14]. Therefore, an optimal approach might involve the target of all three cell types to promote wound healing via synergistic effects.…”

Section: Introductionmentioning

confidence: 99%

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PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

et al. 2020

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Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and reepithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing.Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities.

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Section: Introductionmentioning

confidence: 99%

“…c The change of wound size in different treatment groups. The yellow area is the size of the wound at day 0, and the light blue area is the size of the wound at n (n=,3,7,14) days. d The wound closure rate of each group at 0,3,7,14 days after surgery…”

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confidence: 99%

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

et al. 2020

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“…Tissue miR-21, as described above, is important in several stages of cutaneous wound healing. Several studies have focused on circulating exosomal miR-21 [ 233 ], both the minor miR-21-3p [ 234 ] and the more prevalent miR-21-5p species [ 235 , 236 , 237 ]. In general, EVs with miR-21 improve wound healing through either a combination of enhanced fibroblast function, improved angiogenic activity and/or collagen remodeling by modulating important regulatory effector mRNAs such as MMPs, PTEN, SPRY1, WNT4, β-catenin, TIMP-1, TGF-β1 and THBS1.…”

Section: Circulating and Tissue Micrornas As Biomarkers For The Eamentioning

confidence: 99%

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković

Sørensen

Leal

et al. 2020

Cells

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Wound healing is a complex biological process that is impaired under diabetes conditions. Chronic non-healing wounds in diabetes are some of the most expensive healthcare expenditures worldwide. Early diagnosis and efficacious treatment strategies are needed. microRNAs (miRNAs), a class of 18–25 nucleotide long RNAs, are important regulatory molecules involved in gene expression regulation and in the repression of translation, controlling protein expression in health and disease. Recently, miRNAs have emerged as critical players in impaired wound healing and could be targets for potential therapies for non-healing wounds. Here, we review and discuss the mechanistic background of miRNA actions in chronic wounds that can shed the light on their utilization as specific wound healing biomarkers.

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“…Promotes mesenchymal transition and migration of keratinocytes [21][22][23] Systemic sclerosis (SSc)…”

Section: Ptenmentioning

confidence: 99%

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes

et al. 2020

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In the past decades, the key roles of most microRNA in dermatosis and skin development have been explored one after another. Among them, microRNA-31 (miR-31) has a prominent role in the regulation of keratinocytes. Numerous studies show that miR-31 can positively regulate the proliferation, differentiation and cell activity of keratinocytes via regulating the NF-κB, RAS/MAPK, Notch signaling pathways, and some cytokines. At present, the interaction between miR-31 and the NF-κB signaling pathway in keratinocytes is a hot research topic. The positive feedback loop formed by miR-31 and NF-κB signaling may bring new ideas for the prevention of psoriasis. The abnormal state of keratinocytes is usually the pathological basis of many skin and immune system diseases. Therefore, strengthening the ability to regulate keratinocytes may be a breakthrough for a variety of diseases. At the same time, miR-31's capacity to accelerate wound healing via positively regulating keratinocytes should be further investigated in the treatment of chronic ulcers and trauma.

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Human keratinocyte-derived microvesicle miRNA-21 promotes skin wound healing in diabetic rats through facilitating fibroblast function and angiogenesis

Cited by 79 publications

References 49 publications

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

Mechanistic Actions of microRNAs in Diabetic Wound Healing

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes

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