Adipose‐derived mesenchymal stem cells‐sourced exosomal microRNA‐7846‐3p suppresses proliferation and pro‐angiogenic role of keloid fibroblasts by suppressing neuropilin 2

Author:

Wu Di12,Liu Xiao1,Jin Zhehu2

Affiliation:

1. Department of Dermatology Jilin Central Hospital Jilin China

2. Department of Dermatology Affiliated Hospital of Yanbian University Yanji China

Abstract

AbstractBackgroundExosomes (Exos) and their contained microRNAs (miRNAs) have been emergingly recognized as key regulators in spanning biological processes, including proliferation and angiogenesis.Aim of the studyThis work investigates the function of Exos derived from adipose‐derived mesenchymal stem cells (adMSCs) in viability of keloid fibroblasts (KFs).MethodsAbnormally expressed miRNAs in keloid tissues were screened using the GEO dataset GSE113620. Meanwhile, miRNAs enriched in adMSC‐Exos were predicted by bioinformatics system. Exos were extracted from acquired adMSCs and identified, which were co‐incubated with KFs. Uptake of Exos by KFs was examined by fluorescence staining. Viability, proliferation, and apoptosis of KFs were analyzed by CCK‐8, EdU labeling, and TUNEL assays. Conditioned medium of KFs was collected to stimulate angiogenesis of human umbilical vein endothelial cells (HUVECs). Binding between miR‐7846‐3p and neuropilin 2 (NRP2) was validated by luciferase assay. Protein levels of NRP2 and the Hedgehog pathway molecules were analyzed by western blot analysis.ResultsmiR‐7846‐3p was predicted as an exosomal miRNA aberrantly expressed in keloids. AdMSC‐Exos reduced viability, proliferation, and apoptosis resistance of KFs, and they blocked the angiogenesis of HUVECs. miR‐7846‐3p targeted NRP2 mRNA. miR‐7846‐3p upregulation in KFs suppressed NRP2 expression and reduced the expression of Hedgehog pathway molecules SHH, SMO, and GLI1. Either miR‐7846‐3p inhibition in Exos or NRP2 overexpression in KFs blocked the effects of Exos and restored the viability, proliferation, and pro‐angiogenic role of KFs.ConclusionThis work unravels that adMSC‐Exos‐derived miR‐7846‐3p suppresses NRP2 and inactivates the Hedgehog signaling to reduce proliferation and pro‐angiogenic role of KFs.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Dermatology

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