MiR-23b and miR-133 cotarget TGFβ2/NOTCH1 in dermal fibroblasts and affect hair follicle development in sheep

Abstract Background Wool, which is a pure natural textile fiber raw material, has high economic value and is increasingly favored by modern textile enterprises and consumers. The output of fine wool, especially high-quality superfine wool, in China is far from meeting the processing needs of the textile market. Therefore, improving the yield and quality of wool has always been a focus of research related to fine wool sheep breeding. Wool is produced and controlled by hair follicles (HFs). However, little is known about the mechanisms involved in HF development and regulation. The structure, function and morphogenesis of HFs are complex biological processes. Sheep dermal fibroblasts (SDFs) play a key role in the initial stage of HF development. Analyzing the molecular mechanism that regulates early HF development in superfine wool sheep is of great importance for better understanding the HF morphogenesis process and for the breeding of fine wool sheep. Here, we show that two microRNAs (miRNAs) affect the development of HFs by targeting two genes that are expressed by SDFs. Results On the basis of our previous research, we further found that oar-miR-23b and oar-miR-133 and their cotarget genes TGFβ2 and NOTCH1 were differentially expressed during the six stages of HF development in superfine wool sheep. Overexpression/inhibition of oar-miR-23b and oar-miR-133 in SDFs showed that oar-miR-23b and oar-miR-133 inhibited the proliferation and migration of SDFs and promoted the apoptosis of SDFs through TGFβ2 and NOTCH1. By analyzing genes that are upstream and downstream of the target genes, we found that oar-miR-23b and oar-miR-133 affected the expression of genes in the TGF-β, Hippo and WNT signaling pathways. Conclusion oar-miR-23b and oar-miR-133 inhibit the proliferation and migration of SDFs by jointly targeting TGFβ2 and NOTCH1, thereby inhibiting the development of super fine wool HFs. Our research provides a molecular marker that can be used to guide the breeding of ultrafine wool sheep.