Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis
Abstract Atopic dermatitis is defined as an intensely systemic inflammation among skin diseases. Exosomes derived from adipose-derived stem cells may be a novel cell-free therapeutic strategy for atopic dermatitis treatment. This study aims to elucidate the possible underlying mechanism of adipose-d...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-34418-y |
| _version_ | 1797811520965443584 |
|---|---|
| author | Chenlong Shi Sujun Pei Ying Ding Congmin Tao Yuanzheng Zhu Ying Peng Wei Li Yangyan Yi |
| author_facet | Chenlong Shi Sujun Pei Ying Ding Congmin Tao Yuanzheng Zhu Ying Peng Wei Li Yangyan Yi |
| author_sort | Chenlong Shi |
| collection | DOAJ |
| description | Abstract Atopic dermatitis is defined as an intensely systemic inflammation among skin diseases. Exosomes derived from adipose-derived stem cells may be a novel cell-free therapeutic strategy for atopic dermatitis treatment. This study aims to elucidate the possible underlying mechanism of adipose-derived stem cells-exosomes harboring microRNA-147a in atopic dermatitis pathogenesis. BALB/c mice treated with Dermatophagoides farinae extract/2,4-dinitrochlorobenzene were defined as a mouse model of atopic dermatitis, either with inflamed HaCaT cells and HUVECs exposed with TNF-α/IFN-γ stimulation were applied for a cell model of atopic dermatitis. The concentrations of IL-1β and TNF-α in the supernatants were examined by ELISA. Cell viability and migration were assessed by MTT and Transwell assay. The apoptosis was examined using flow cytometry and TUNEL staining. The tube formation assay was employed to analyzed angiogenesis. The molecular regulations among miR-147a, MEF2A, TSLP and VEGFA were confirmed using luciferase reporter assay, either with ChIP. microRNA-147a was markedly downregulated in the serum and skin samples of atopic dermatitis mice, of which overexpression remarkably promoted HaCaT cell proliferation, meanwhile inhibiting inflammatory response and cell apoptosis. microRNA-147a in adipose-derived stem cells was subsequently overexpressed, and exosomes (Exos-miR-147a mimics) were collected. Functionally, exos-microRNA-147a mimics attenuated TNF-α/IFN-γ-induced HaCaT cell inflammatory response and apoptosis, and suppressed HUVECs angiogenesis. Encouraging, molecular interaction experiments revealed that exosomal microRNA-147a suppressed TNF-α/IFN-γ-induced HUVECs angiogenesis by targeting VEGFA, and exosomal microRNA-147a repressed HaCaT cells inflammatory injury through the MEF2A-TSLP axis. Mechanistically, exosomal microRNA-147a repressed pathological angiogenesis and inflammatory injury during atopic dermatitis progression by targeting VEGFA and MEF2A-TSLP axis. microRNA-147a-overexpressing adipose-derived stem cells-derived exosomes suppressed pathological angiogenesis and inflammatory injury in atopic dermatitis by targeting VEGFA and MEF2A-TSLP axis. |
| first_indexed | 2024-03-13T07:23:55Z |
| format | Article |
| id | doaj.art-06dc36365e4c4c89950bbe411fc2baa5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:23:55Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-06dc36365e4c4c89950bbe411fc2baa52023-06-04T11:27:14ZengNature PortfolioScientific Reports2045-23222023-06-0113111410.1038/s41598-023-34418-yExosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitisChenlong Shi0Sujun Pei1Ying Ding2Congmin Tao3Yuanzheng Zhu4Ying Peng5Wei Li6Yangyan Yi7Department of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of Plastic Surgery, The Second Affiliated Hospital of Nanchang UniversityAbstract Atopic dermatitis is defined as an intensely systemic inflammation among skin diseases. Exosomes derived from adipose-derived stem cells may be a novel cell-free therapeutic strategy for atopic dermatitis treatment. This study aims to elucidate the possible underlying mechanism of adipose-derived stem cells-exosomes harboring microRNA-147a in atopic dermatitis pathogenesis. BALB/c mice treated with Dermatophagoides farinae extract/2,4-dinitrochlorobenzene were defined as a mouse model of atopic dermatitis, either with inflamed HaCaT cells and HUVECs exposed with TNF-α/IFN-γ stimulation were applied for a cell model of atopic dermatitis. The concentrations of IL-1β and TNF-α in the supernatants were examined by ELISA. Cell viability and migration were assessed by MTT and Transwell assay. The apoptosis was examined using flow cytometry and TUNEL staining. The tube formation assay was employed to analyzed angiogenesis. The molecular regulations among miR-147a, MEF2A, TSLP and VEGFA were confirmed using luciferase reporter assay, either with ChIP. microRNA-147a was markedly downregulated in the serum and skin samples of atopic dermatitis mice, of which overexpression remarkably promoted HaCaT cell proliferation, meanwhile inhibiting inflammatory response and cell apoptosis. microRNA-147a in adipose-derived stem cells was subsequently overexpressed, and exosomes (Exos-miR-147a mimics) were collected. Functionally, exos-microRNA-147a mimics attenuated TNF-α/IFN-γ-induced HaCaT cell inflammatory response and apoptosis, and suppressed HUVECs angiogenesis. Encouraging, molecular interaction experiments revealed that exosomal microRNA-147a suppressed TNF-α/IFN-γ-induced HUVECs angiogenesis by targeting VEGFA, and exosomal microRNA-147a repressed HaCaT cells inflammatory injury through the MEF2A-TSLP axis. Mechanistically, exosomal microRNA-147a repressed pathological angiogenesis and inflammatory injury during atopic dermatitis progression by targeting VEGFA and MEF2A-TSLP axis. microRNA-147a-overexpressing adipose-derived stem cells-derived exosomes suppressed pathological angiogenesis and inflammatory injury in atopic dermatitis by targeting VEGFA and MEF2A-TSLP axis.https://doi.org/10.1038/s41598-023-34418-y |
| spellingShingle | Chenlong Shi Sujun Pei Ying Ding Congmin Tao Yuanzheng Zhu Ying Peng Wei Li Yangyan Yi Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis Scientific Reports |
| title | Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| title_full | Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| title_fullStr | Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| title_full_unstemmed | Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| title_short | Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| title_sort | exosomes with overexpressed mir 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis |
| url | https://doi.org/10.1038/s41598-023-34418-y |
| work_keys_str_mv | AT chenlongshi exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT sujunpei exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT yingding exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT congmintao exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT yuanzhengzhu exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT yingpeng exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT weili exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis AT yangyanyi exosomeswithoverexpressedmir147asuppressangiogenesisandinfammatoryinjuryinanexperimentalmodelofatopicdermatitis |