Apratyramide, a Marine-Derived Peptidic Stimulator of VEGF-A and Other Growth Factors with Potential Application in Wound Healing

作者：Cai, Weijing; Salvador-Reyes, Lilibeth A.; Zhang, Wei; Chen, Qi-Yin; Matthew, Susan; Ratnayake, Ranjala; Seo, Soo Jung; Dolles, Simon; Gibson, Daniel J.; Paul, Valerie J.; Luesch, Hendrik^*

来源：ACS Chemical Biology, 2018, 13(1): 91-99.

DOI：10.1021/acschembio.7b00827

• UNFOLDED PROTEIN RESPONSE
• TRANSCRIPTION FACTOR XBP-1
• PLASMA-CELL DIFFERENTIATION
• IN-VITRO
• EPIDERMAL-KERATINOCYTES
• ANGIOGENESIS
• EXPRESSION
• MICE
• SKIN
• FIBROBLASTS

A novel linear depsipeptide enriched with tyrosine-derived moieties, termed apratyramide, was isolated from an apratoxin-producing cyanobacterium. The structure was determined using a combination of NMR spectroscopy) mass spectrometry, and chiral analysis of the acid hydrolyzate and-confirmed by total synthesis. Apratyramide up-regulated. multiple growth factors at the transcript level in human keratinocyte (HaCaT) cells and induced the secretion of vascular endothelial growth factor A (VEGF-A) from HaCaT cells, suggesting the compound's potential wound-healing properties through growth factor induction. Transcriptome analysis and sequential validation supported the hypothesis and indicated its mode of action (MOA) through the unfolded protein response (UPR) pathway, which is functionally related to, wound healing and. angiogenesis. The conditioned medium of HaCaT cells treated with apratyramide induced angiogenesis in vitro. An ex vivo rabbit corneal epithelial model was applied to confirm the VEGF-A induction in this wound-healing model.

• 出版日期2018-1
• 单位复旦大学