MiR-143 Targeting CUX1 to Regulate Proliferation of Dermal Papilla Cells in Hu Sheep.

Tingyan Hu,Wei Sun,Joram M Mwacharo,Aynalem Haile,Sainan Huang,Xiaoyang Lv,Tesfaye Getachew,Shanhe Wang

doi:10.3390/genes12122017

Abstract

Wool curvature is the determining factor for lambskin quality of Hu lambs. However, the molecular mechanism of wool curvature formation is not yet known. miRNA has been proved to play an important role in hair follicle development, and we have discovered a differentially expressed miRNA, miR-143, in hair follicles of different curl levels. In this study, we first examined the effects of miR-143 on the proliferation and cell cycle of dermal papilla cells using CCK8, EdU and flow cytometry and showed that miR-143 inhibited the proliferation of dermal papilla cells and slowed down the cell cycle. Bioinformatics analysis was performed to predict the target genes KRT71 and CUX1 of miR-143, and both two genes were expressed at significantly higher levels in small waves than in straight lambskin wool (p < 0.05) as detected by qPCR and Western blot (WB). Then, the target relationships between miR-143 and KRT71 and CUX1 were verified through the dual-luciferase assay in 293T cells. Finally, after overexpression and suppression of miR-143 in dermal papilla cells, the expression trend of CUX1 was contrary to that of miR-143. Meanwhile, KRT71 was not detected because KRT71 was not expressed in dermal papilla cells. Therefore, we speculated that miR-143 can target CUX1 to inhibit the proliferation of dermal papilla cells, while miR-143 can target KRT71 to regulate the growth and development of hair follicles, so as to affect the development of hair follicles and ultimately affect the formation of wool curvature.

Highlights

In natural its state, a wool fiber forms a regular curl along its longitudinal axis, a characteristic commonly known as wool curvature
According to the pattern width and the degree of wool curvature, lambskins are divided into four types, including small waves, medium waves, large waves and straight wool, of which small waves show the best quality and straight wool shows the worst
Based on biology and genetics, Westgate et al [31] proposed a valuable opinion that genetic factors and cellular processes influence the molecular mechanisms of genes and the differentiation of some hair follicle cells, determining the hair follicle morphogenesis, leading to the phenomenon of hair bending

Summary

Introduction

A wool fiber forms a regular curl along its longitudinal axis, a characteristic commonly known as wool curvature. The growth of hair follicles in the skin causes the wool to bend, resulting in the formation of different wavy patterns of lambskin. The hair follicle is a specific skin appendage that has the ability to grow periodically. Traits such as the shape, type and color of wool are closely associated with the development and cycle of hair follicles. The Wnt/β-catenin, TGF-β/BMP and other signaling pathways form a complex network to control the formation and cyclic development of hair follicles, resulting in different wool wavy pattern phenotypes [1–4]. Previous research has revealed that the dermal papilla cells are the regulatory center in the development of hair follicles, and the number and type of papilla cells are decisive for the growth of hair follicles, the type and curvature of wool [5,6]

Methods

Results

Conclusion