Apoptotic bodies extracted from adipose mesenchymal stem cells carry microRNA-21–5p to induce M2 polarization of macrophages and augment skin wound healing by targeting KLF6

Li, Jianrui; Wei, Chuan‐Yuan; Yang, Yang; Gao, Zixu; Guo, Zheng; Qi, Fazhi

doi:10.1016/j.burns.2021.12.010

Cited by 26 publications

(17 citation statements)

References 54 publications

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“…Wound healing is a complex process including 4 phases of hemostasis, inflammation, proliferation, and remodeling. This procedure involves a variety of cell types such as neutrophils, macrophages, mast cells, monocytes, Th1 cells, Th17 cells, and regulatory T cells which also have impacts on wound healing 40–42 . Although DETCs are the only T cell subgroup found in the epidermis, Vγ4 T cells residing at the dermis can enter the epidermis after skin injury 3,43 .…”

Section: Discussionmentioning

confidence: 99%

“…This procedure involves a variety of cell types such as neutrophils, macrophages, mast cells, monocytes, Th1 cells, Th17 cells, and regulatory T cells which also have impacts on wound healing. [40][41][42] Although DETCs are the only T cell subgroup found in the epidermis, Vγ4 T cells residing at the dermis can enter the epidermis after skin injury. 3,43 Whether let-7f-5p regulates these cells in wound healing needs to be clarified.…”

Section: Discussionmentioning

confidence: 99%

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IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells

Wang

et al. 2022

Journal of Leukocyte Biology

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Dendritic epidermal T cells (DETCs) are the main source of insulin‐like growth factor‐1 (IGF‐1) in epidermal tissue, which promote re‐epithelialization and wound healing. In refractory wounds, IL‐1β has been shown to activate NF‐κB and suppress IGF‐1 expression in DETCs. Nevertheless, the underlying mechanisms remain unclear. In this study, chromatin immunoprecipitation analysis revealed that IL‐1β did not inhibit NF‐κB binding to IGF‐1 promoter, indicating that IL‐1β/NF‐κB may suppress IGF‐1 expression by alternative mechanisms. MiRNAs negatively regulate gene expression predominantly by base pairing to the 3′ untranslation region (UTR) of target mRNAs. Let‐7f‐5p, miR‐1a‐3p, and miR‐98‐5p have been identified as IGF‐1‐specific miRNAs that can bind directly to the 3′UTR of IGF‐1 mRNA and dysregulate IGF‐1 mRNA and protein levels. In IL‐1β‐treated epidermis around wounds or DETCs in vitro, NF‐κB promoted the expression of let‐7f‐5p, and IGF‐1 expression was impeded via NF‐κB/let‐7f‐5p pathway. As pre‐let‐7f‐5p, let‐7f‐1 is located in the 3′UTR of LOC118568094, and let‐7f‐2 is located in the intron of HUWE1. We discovered that NF‐κB p65 bound to the promoters of LOC118568094 and HUWE1 to accelerate let‐7f‐5p expression, but NF‐κB p65 did not affect the methylation levels of LOC118568094 and HUWE1 CpG islands. Injections of Let‐7f‐5p antagomir into IL‐1β‐treated and ischemic wound margins restored IGF‐1 secretion in DETCs and promoted wound healing. In conclusion, we demonstrated that NF‐κB signaling pathway activated by IL‐1β could increase let‐7f‐5p expression to inhibit IGF‐1 production in DETCs and delay wound healing. And let‐7f‐5p antagomir utilized in wound margin could effectively promote refractory wound healing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells

Wang

et al. 2022

Journal of Leukocyte Biology

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“…Tumor-associated macrophages (TAMs) comprise an important part of the TME, are predominantly M2-polarized, and play a key role in DLBCL progression [ 469 , 470 , 471 , 472 ]. Compelling evidence in various cancer entities underlines the impact of miR-21-5p in driving M2 polarization of macrophages and TAMs [ 473 , 474 , 475 , 476 ], whereas inhibition or depletion of miR-21 reversed M2 polarization back to the M1 phenotype [ 477 , 478 , 479 ]. Remarkably, miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy [ 477 ].…”

Section: Exosomal Micrornas In the Pathogenesis Of Dlbclmentioning

confidence: 99%

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

Melnik

Stadler

Weiskirchen

et al. 2023

IJMS

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Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.

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“…A study by Li et al examined the apoptotic bodies of AD-MSCs and found abundant expression of microRNA (miRNA)-21-5p, which was found to target Kruppel-like factor 6 (KLF6). The macrophages overexpressing KLF6 were inhibited to undergo polarization to the M2 phenotype; therefore, targeting KLF6 with miR-21-5p resulted in augmented skin-wound healing [ 78 ].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

Molnar

Pavelić²,

Vrdoljak

et al. 2022

Genes

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With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.

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Apoptotic bodies extracted from adipose mesenchymal stem cells carry microRNA-21–5p to induce M2 polarization of macrophages and augment skin wound healing by targeting KLF6

Cited by 26 publications

References 54 publications

IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells

IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

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