College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Genes (Basel). 2022 Apr 12;13(4):679. doi: 10.3390/genes13040679.
Mammalian hair formation is critically determined by the growth of hair follicles (HF). MiRNAs are crucial in the periodic development of hair follicles; they maintain epidermal homeostasis by targeting genes and influencing the activity of signaling pathways and related regulators. Our study discovered miR-129-5p to be overexpressed in the skin of Angora rabbits during catagen, and was negatively correlated with HOXC13 expression (Pearson’s R = −0.313, p < 0.05). The dual-Luciferase reporter gene detection system and Western blotting confirmed that miR-129-5p targeted HOXC13. In addition, miR-129-5p overexpression was found to significantly inhibit the expression of hair follicle development-related genes (HFDRGs), such as BCL2, WNT2, CCND1, and LEF1 (p < 0.01), and promoted the expression of SFRP2, TGF-β1, and FGF2 (p < 0.01), which was the same as the knockdown of HOXC13. In contrast, the knockout of miR-129-5p was the opposite, and it demonstrated similar results to the overexpression of HOXC13. CCK8 and flow cytometry demonstrated that miR-129-5p mimics significantly promoted the apoptosis of dermal papilla cells (DPCs) and inhibited proliferation (p < 0.01), while the inhibitor was found to reduce the apoptosis of DPCs and promote proliferation (p < 0.01). These results showed that miR-129-5p can participate in the periodic development of HF by targeting HOXC13, and it can induce apoptosis and inhibit proliferation of DPCs. These results will help to understand the role and mechanism of miR-129-5p in the periodic development of HF, and will provide support for subsequent studies, not only providing a theoretical basis for genetically improving the quality of hair in animals in the future, but also a new theory and method for diagnosing and treating hair loss in humans.
哺乳动物的毛发形成主要由毛囊（HF）的生长决定。miRNA 在毛囊的周期性发育中起着至关重要的作用；它们通过靶向基因并影响信号通路和相关调节剂的活性，来维持表皮的内稳态。我们的研究发现，miR-129-5p 在安哥拉兔的生长期过度表达，并与 HOXC13 的表达呈负相关（皮尔逊 R = -0.313，p < 0.05）。双荧光素酶报告基因检测系统和 Western blot 证实 miR-129-5p 靶向 HOXC13。此外，发现过表达 miR-129-5p 可显著抑制毛囊发育相关基因（HFDRGs）的表达，如 BCL2、WNT2、CCND1 和 LEF1（p < 0.01），并促进 SFRP2、TGF-β1 和 FGF2 的表达（p < 0.01），这与 HOXC13 的敲低相同。相反，miR-129-5p 的敲除则相反，其结果与 HOXC13 的过表达相似。CCK8 和流式细胞术表明，miR-129-5p 模拟物可显著促进真皮乳头细胞（DPC）的凋亡并抑制增殖（p < 0.01），而抑制剂则可减少 DPC 的凋亡并促进增殖（p < 0.01）。这些结果表明，miR-129-5p 可以通过靶向 HOXC13 参与 HF 的周期性发育，并可以诱导 DPC 的凋亡和抑制增殖。这些结果将有助于了解 miR-129-5p 在 HF 周期性发育中的作用和机制，并为后续研究提供支持，不仅为未来在动物中通过基因改良毛发质量提供理论依据，也为人类脱发的诊断和治疗提供新的理论和方法。
