Melatonin regulates the mitogen-activated protein kinase ( MAPK ) pathway via the circMPP5-miR-211-MAPK3 axis to induce secondary hair follicle differentiation and development in newborn Cashmere goat kids

Abstract Background The quality and yield of Cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of Cashmere goats. The higher the density of secondary hair follicles, the higher the quality and yield of Cashmere from the fleece. Development of secondary hair follicles commences in the embryonic stage of life and is completed six months after birth. Preliminary experimental results from our laboratory showed that melatonin (MT) treatment of goat kids after their birth could increase the density of secondary hair follicles and, thus, improve the subsequent yield and quality of Cashmere. These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein, and from a reduction in apoptosis. The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis. Results MT had no adverse effect on the growth performance of Cashmere kids but significantly improved the character of the secondary hair follicles and the quality of Cashmere, and this dominant effect continued to the second year. Melatonin promotes the proliferation of secondary hair follicle cells at an early age. Secondary hair follicles in the MT group formation was earlier than in the control group in the second year. The genome-wide data results involved KEGG analysis of 1044 DEmRNAs, 91 DElncRNAs, 1054 DEcircRNAs, and 61 DEmiRNAs which revealed that the MAPK signaling pathway is involved in the development of secondary hair follicles, with key genes (FGF2, FGF21, FGFR3, MAPK3 (ERK1)) being up-regulated and expressed. We also found that the circMPP5 could combine with miR-211 and regulate the expression of MAPK3. Conclusions We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5-miR-211-MAPK3 axis to induce the differentiation and proliferation of secondary hair follicle cells. In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells. Collectively, these events increase the numbers of secondary hair follicles, thus improving the production of Cashmere from these goats.