Background
Senescent fibroblasts play a role in aging pigmentation. In our previous RNA sequencing data in senescent fibroblasts, the Growth differentiation factor 15 (GDF-15) gene was found to be significantly upregulated.
Objective
We investigated the role of senescent fibroblast-derived GDF15 in the regulation of human pigmentation.
Methods
Normal human melanocytes were co-cultured with fibroblasts infected with GDF15 lenti-virus or sh-GDF15 and melanogenesis was analyzed. The pigmentation were also assessed in the ex vivo skin culture.
Results
The melanin contents and tyrosinase activity were significantly increased in melanocytes co-cultured with fibroblasts infected with GDF15 lenti-virus. The mRNA and protein expression levels of melanogenesis-associated proteins, microphthalmia-associated transcription factor (MITF) and tyrosinase were significantly up-regulated. The GDF15 stimulated b-catenin signaling in melanocytes. Consistently, the pigmentation were significantly reduced in melanocytes co-cultured with fibroblasts infected with sh-GDF15. The stimulatory action of GDF15 in pigmentation was further confirmed in ex vivo cultured skin.
Conclusion
Senescent fibroblast-derived GDF15 stimulates skin pigmentation and it may play a role in the aging pigmentation.
