Edible Bird’s Nest, an Asian Health Food Supplement, Possesses Moisturizing Effect by Regulating Expression of Filaggrin in Skin Keratinocyte

Edible bird’s nest (EBN) has been consumed as a Chinese delicacy for hundreds of years; the functions of which have been proposed to prevent lung disease, strengthen immune response, and restore skin youthfulness. To support the skin function of EBN, the water extract and the enzymatic digest of EBN with enriched digested peptides were tested in cultured keratinocyte, HaCaT cell line. The effects of EBN extract and digest in inducing proteins crucial for skin moisturizing were determined in both in vitro and ex vivo models. In cultured keratinocytes, the expressions of S100-fused type proteins contributing to skin barrier function in the stratum corneum, e.g. filaggrin and filaggrin-2, were determined in both mRNA and protein levels, which were markedly induced in the treatment of EBN extract or digest. The EBN-induced gene transcriptions of filaggrin and filaggrin-2 were mediated by activation of p38 MAPK pathway and various transcription factors, e.g. GATA3, PPARα, PPARβ, and PPARγ: these transcriptional factors were markedly activated by the digested products of EBN, as compared to the extract, in cultured keratinocytes. By using atomic force microscopy (AFM), the EBN-treated keratinocyte was shown to have more liquid-like morphology, as compared to a control cell. The EBN digest showed better induction on these moisturizing effects as compared to the extract. These lines of evidence therefore suggested the water moisturizing effect of EBN in skin function.

Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution

Humans sweat to cool their bodies and have by far the highest eccrine sweat gland density among primates. Humans’ high eccrine gland density has long been recognized as a hallmark human evolutionary adaptation, but its genetic basis has been unknown. In humans, expression of the Engrailed 1 (EN1) transcription factor correlates with the onset of eccrine gland formation. In mice, regulation of ectodermal En1 expression is a major determinant of natural variation in eccrine gland density between strains, and increased En1 expression promotes the specification of more eccrine glands. Here, we show that regulation of EN1 has evolved specifically on the human lineage to promote eccrine gland formation. Using comparative genomics and validation of ectodermal enhancer activity in mice, we identified a human EN1 skin enhancer, hECE18. We showed that multiple epistatically interacting derived substitutions in the human ECE18 enhancer increased its activity compared with nonhuman ape orthologs in cultured keratinocytes. Repression of hECE18 in human cultured keratinocytes specifically attenuated EN1 expression, indicating this element positively regulates EN1 in this context. In a humanized enhancer knock-in mouse, hECE18 increased developmental En1 expression in the skin to induce the formation of more eccrine glands. Our study uncovers a genetic basis contributing to the evolution of one of the most singular human adaptations and implicates multiple interacting mutations in a single enhancer as a mechanism for human evolutionary change.