López-Mejía Alejandro, Briseño-Díaz Paola, Robles-Flores Martha
Department of Biochemistry, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, México.
Department of Biochemistry, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, México.
Biochim Biophys Acta Mol Cell Res. 2025 Oct;1872(7):120007. doi: 10.1016/j.bbamcr.2025.120007. Epub 2025 Jun 11.
Hypoxia-inducible factors (HIFs) are master regulators of cellular adaptation to hypoxia in both disease and normal physiological conditions. HIFs consist of two subunits: the oxygen-sensitive alpha (α) and the constitutively expressed beta (β). The three oxygen-dependent alpha subunits-HIF-1α, HIF-2α, and HIF-3α-encoded by distinct genes are crucial for regulating cellular responses to hypoxia in various vertebrates, including humans. Much of our understanding of HIFs is based on studies on HIF-1α and HIF-2α subunits. Recent studies have shown that, although HIF-3α is the least studied member, it may also play essential roles in the development of human diseases, including cancer, cardiovascular and respiratory diseases, metabolic disorders, and other pathological processes. In this review, we focus on how HIF-3α overexpression is associated with various human diseases, aiming to better understand its role in human pathophysiology and its potential use as a therapeutic target.
缺氧诱导因子（HIFs）是细胞在疾病和正常生理条件下适应缺氧的主要调节因子。HIFs由两个亚基组成：氧敏感的α亚基和组成型表达的β亚基。由不同基因编码的三种氧依赖性α亚基——HIF-1α、HIF-2α和HIF-3α——对于调节包括人类在内的各种脊椎动物细胞对缺氧的反应至关重要。我们对HIFs的大部分了解都基于对HIF-1α和HIF-2α亚基的研究。最近的研究表明，尽管HIF-3α是研究最少的成员，但它可能在包括癌症、心血管和呼吸系统疾病、代谢紊乱及其他病理过程在内的人类疾病发展中也发挥着重要作用。在这篇综述中，我们重点关注HIF-3α过表达如何与各种人类疾病相关联，旨在更好地了解其在人类病理生理学中的作用及其作为治疗靶点的潜在用途。
