| First Author | Li G | Year | 2022 |
| Journal | J Invest Dermatol | PubMed ID | 35413292 |
| Mgi Jnum | J:325669 | Mgi Id | MGI:7280567 |
| Doi | 10.1016/j.jid.2022.03.026 | Citation | Li G, et al. (2022) Aging-Conferred SIRT7 Decline Inhibits Rosacea-Like Skin Inflammation by Modulating Toll-Like Receptor 2NF-kappaB Signaling. J Invest Dermatol |
| abstractText | Rosacea is a chronic inflammatory skin disorder that manifests abnormal enhanced sensitivity to environmental stimuli. The decreased prevalence of rosacea in aged population has been reported, but the underlying mechanism is unclear. In this study, we confirm that the rosacea-like skin inflammation induced by cathelicidin LL37 is alleviated in aged mice and mice with progeria. Primary mouse keratinocytes isolated from aged mice and human dermal fibroblasts that undergo senescence present a much lower sensitivity to proinflammatory stimuli. Mechanistically, toll-like receptor 2 (TLR2) is downregulated in the skin of both aged population and mice. Knockdown of TLR2 in young human dermal fibroblasts mimics the attenuated immune response to LL37 and TNF-alpha evidenced in aged human dermal fibroblasts, whereas overexpression of TLR2 in aged human dermal fibroblasts rescued this attenuation. At the molecular level, in response to inflammatory stimuli, SIRT7 mediates the upregulation of TLR2, which promotes the activation of NF-kappaB signaling. The decay of SIRT7 confers an age-related decline of TLR2NF-kappaB signaling. Although the overexpression of exogenous Sirt7 abrogates skin immune reactivity reduction in aged mice, loss of Sirt7 alleviates the rosacea-like features in mice. Thus, we reveal a SIRT7TLR2NF-kappaB axis that can be targeted for the improvement of rosacea. |
