期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126860
关键词
autophagy; cGMP; fibroblasts; mass spectrometry; nitric oxide; NO; proteomics; skin; sildenafil; wound healing
资金
- Innosuisse [29588.1 IP-LS]
- Swiss National Science Foundation [310030_184781]
- University of Fribourg
- Canton of Fribourg
- Swiss National Science Foundation (SNF) [310030_184781] Funding Source: Swiss National Science Foundation (SNF)
Wound healing pathologies are a growing issue in aging societies. TOP-N53, a small molecule that supports wound healing, activates the autophagy pathway in skin fibroblasts.
Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce. Here, we performed expression proteomics to study the effects of the small molecule TOP-N53 on primary human skin fibroblasts and keratinocytes. TOP-N53 is a dual-acting nitric oxide donor and phosphodiesterase-5 inhibitor increasing cGMP levels to support proper wound healing. In contrast to keratinocytes, which did not exhibit global proteome alterations, TOP-N53 had profound effects on the proteome of skin fibroblasts. In fibroblasts, TOP-N53 activated the cytoprotective, lysosomal degradation pathway autophagy and induced the expression of the selective autophagy receptor p62/SQSTM1. Thus, activation of autophagy might in part be responsible for beneficial effects of TOP-N53.
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