Cell proliferation and migration mechanism of caffeoylserotonin and serotonin via serotonin 2B receptor in human keratinocyte HaCaT cells

Abstract

Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-κB/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration.

Positive Promoting Effects of Smilax China Flower Absolute on the Wound Healing/Skin Barrier Repair‐Related Responses of HaCaT Human Skin Keratinocytes

“…During skin wound healing, the migration and proliferation of keratinocytes can be mediated by various signaling pathways. Previous reports show that Akt signal activation participates in the regulations of various cellular events, such as cell survival, growth, proliferation, and migration [26,33] and that the Akt pathway is involved in the migration and proliferation of keratinocytes [5,24,34] . In the present study, we found that SCF absolute at concentrations of 100 and 150 μg/mL increased Akt phosphorylation in HaCaT cells, thus indicating, that it stimulated migration and proliferation via Akt activation.…”

“…The MAPK family is conventionally divided into three subgroups, namely, Erk1/2, c‐Jun NH2‐terminal kinase (JNK), and p38 MAPK [35] . It has been shown downregulation of the Erk1/2 signal reduces keratinocyte migration and proliferation, [36,37] and that increased Erk1/2 phosphorylation is positively associated with keratinocyte migration and proliferation [24,34] . p38 MAPK phosphorylation has also been reported to mediate keratinocyte proliferation and migration [25,38] .…”

The Multifaceted Role of Serotonin in Intestinal Homeostasis

“…In accord, activation of HTR4 increased cell proliferation in intestinal crypts and promoted cell migration while reducing oxidative stress and apoptosis in Caco2 cells [127]. Similar effects on cell proliferation have been described in a keratinocyte HaCaT cell line, hepatic stellate cells, and pulmonary arterial smooth muscle cells [139][140][141]. These findings suggest that HTR activation could augment disease characterized by mucosal damage like IBD through stimulation of epithelial cell proliferation and hence mucosal healing.…”

Isoegomaketone from Perilla frutescens (L.) Britt Stimulates MAPK/ERK Pathway in Human Keratinocyte to Promote Skin Wound Healing

“…Cyclins are a family of proteins that regulate cell cycle progression by activating cyclin-dependent kinases (CDKs) [ 37 ]. Given the significance of the cyclin pathway in wound healing, the effects of IK on the regulation of cyclin families, especially cyclin D1 regulated by the MAPK/ERK pathway, should be investigated [ 38 , 39 ]. These results suggested that IK stimulates the MAPK/ERK pathway in keratinocytes, which is crucial in wound healing processes.…”