高原环境下牦牛皮肤适应性的分子调控机制

牦牛的特殊生长环境包括低温、低氧、强辐射等因素，生长环境的变化必将引起相关基因和蛋白表达的变化，从而使组织结构发生特异性变化以适应环境刺激。本课题组前期研究发现，与生活在低海拔地区的黄牛相比，牦牛皮肤真皮层厚、毛细血管数量多、毛囊数量多，提示牦牛在高原环境的影响下其皮肤结构表现出适应性的改变。TGF-β1和CTGF作为促进成纤维细胞增殖和胶原分泌的因子，二者的表达均受HIF-1α的调控；同时，HIF-1α调控下的VEGF在毛细血管的再生中发挥重要的作用。Leptin和APN是新近发现参与调控毛囊周期的两个重要因子。因此，本课题拟以牦牛为研究对象，探讨HIF-1α/TGF-β1/CTGF信号通路对真皮成纤维细胞增殖及胶原合成的影响，HIF-1α/VEGF对皮肤毛细血管生成的影响，以及Leptin和APN对毛囊周期影响的分子调控，最终阐明高原环境下牦牛皮肤形态学适应性的分子调控机制。

The special growth environment of yak includes low temperature, low oxygen, and ultraviolet radiations among other factors. These factors will inevitably lead to changes in related genes and the expression of proteins, which makes the tissue structure change specifically to adapt to the environmental stimulation. In our previous study, we found that compared with yellow cattle living in low-altitude areas, the yaks’ skin dermis is thicker, with more capillaries and hair follicles, suggesting that the yaks have an adaptive change in their skin structure under the influence of the plateau environment. TGF-β1 and CTGF are factors that promote fibroblast proliferation and collagen secretion, both of which are regulated by HIF-1α. Meanwhile, HIF-1α also regulates VEGF which plays an important role in capillary regeneration. Leptin and APN are two important factors which were recently found to be involved in the regulation of hair follicle cycle. Therefore, taking yak as the research object, at the gene, protein, and cellular level, we discuss the effects of HIF-1α/TGF-β1/CTGF signaling pathway on proliferation and collagen synthesis of dermal fibroblasts, HIF-1α/VEGF influence on skin capillary angiogenesis, low oxygen and ultraviolet radiation on the secretion of adipocytokines Leptin and APN, as well as effects of Leptin and APN on hair follicle cycle. Finally, we elucidated the molecular regulation mechanism of morphological adaptation of yak skin in the plateau environment.