The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts
The skin produces a plethora of antimicrobial peptides that not only show antimicrobial activities against pathogens but also exhibit various immunomodulatory functions. Human β-defensins (hBDs) are the most well-characterized skin-derived antimicrobial peptides and contribute to diverse biological...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8800 |
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| author | Yoshie Umehara Miho Takahashi Hainan Yue Juan Valentin Trujillo-Paez Ge Peng Hai Le Thanh Nguyen Ko Okumura Hideoki Ogawa François Niyonsaba |
| author_facet | Yoshie Umehara Miho Takahashi Hainan Yue Juan Valentin Trujillo-Paez Ge Peng Hai Le Thanh Nguyen Ko Okumura Hideoki Ogawa François Niyonsaba |
| author_sort | Yoshie Umehara |
| collection | DOAJ |
| description | The skin produces a plethora of antimicrobial peptides that not only show antimicrobial activities against pathogens but also exhibit various immunomodulatory functions. Human β-defensins (hBDs) are the most well-characterized skin-derived antimicrobial peptides and contribute to diverse biological processes, including cytokine production and the migration, proliferation, and differentiation of host cells. Additionally, hBD-3 was recently reported to promote wound healing and angiogenesis, by inducing the expression of various angiogenic factors and the migration and proliferation of fibroblasts. Angiogenin is one of the most potent angiogenic factors; however, the effects of hBDs on angiogenin production in fibroblasts remain unclear. Here, we investigated the effects of hBDs on the secretion of angiogenin by human dermal fibroblasts. Both in vitro and ex vivo studies demonstrated that hBD-1, hBD-2, hBD-3, and hBD-4 dose-dependently increased angiogenin production by fibroblasts. hBD-mediated angiogenin secretion involved the epidermal growth factor receptor (EGFR), Src family kinase, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-kappa B (NF-κB) pathways, as evidenced by the inhibitory effects of specific inhibitors for these pathways. Indeed, we confirmed that hBDs induced the activation of the EGFR, Src, JNK, p38, and NF-κB pathways. This study identified a novel role of hBDs in angiogenesis, through the production of angiogenin, in addition to their antimicrobial activities and other immunomodulatory properties. |
| first_indexed | 2024-03-09T10:07:09Z |
| format | Article |
| id | doaj.art-24d1b76776ac4fc8983c9782002da542 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:07:09Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24d1b76776ac4fc8983c9782002da5422023-12-01T22:58:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315880010.3390/ijms23158800The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal FibroblastsYoshie Umehara0Miho Takahashi1Hainan Yue2Juan Valentin Trujillo-Paez3Ge Peng4Hai Le Thanh Nguyen5Ko Okumura6Hideoki Ogawa7François Niyonsaba8Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanThe skin produces a plethora of antimicrobial peptides that not only show antimicrobial activities against pathogens but also exhibit various immunomodulatory functions. Human β-defensins (hBDs) are the most well-characterized skin-derived antimicrobial peptides and contribute to diverse biological processes, including cytokine production and the migration, proliferation, and differentiation of host cells. Additionally, hBD-3 was recently reported to promote wound healing and angiogenesis, by inducing the expression of various angiogenic factors and the migration and proliferation of fibroblasts. Angiogenin is one of the most potent angiogenic factors; however, the effects of hBDs on angiogenin production in fibroblasts remain unclear. Here, we investigated the effects of hBDs on the secretion of angiogenin by human dermal fibroblasts. Both in vitro and ex vivo studies demonstrated that hBD-1, hBD-2, hBD-3, and hBD-4 dose-dependently increased angiogenin production by fibroblasts. hBD-mediated angiogenin secretion involved the epidermal growth factor receptor (EGFR), Src family kinase, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-kappa B (NF-κB) pathways, as evidenced by the inhibitory effects of specific inhibitors for these pathways. Indeed, we confirmed that hBDs induced the activation of the EGFR, Src, JNK, p38, and NF-κB pathways. This study identified a novel role of hBDs in angiogenesis, through the production of angiogenin, in addition to their antimicrobial activities and other immunomodulatory properties.https://www.mdpi.com/1422-0067/23/15/8800human β-defensin (hBD)dermal fibroblastangiogeninangiogenesis |
| spellingShingle | Yoshie Umehara Miho Takahashi Hainan Yue Juan Valentin Trujillo-Paez Ge Peng Hai Le Thanh Nguyen Ko Okumura Hideoki Ogawa François Niyonsaba The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts International Journal of Molecular Sciences human β-defensin (hBD) dermal fibroblast angiogenin angiogenesis |
| title | The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts |
| title_full | The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts |
| title_fullStr | The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts |
| title_full_unstemmed | The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts |
| title_short | The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts |
| title_sort | antimicrobial peptides human β defensins induce the secretion of angiogenin in human dermal fibroblasts |
| topic | human β-defensin (hBD) dermal fibroblast angiogenin angiogenesis |
| url | https://www.mdpi.com/1422-0067/23/15/8800 |
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