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HIF-1alpha 在 UVB 诱导的表皮过度增生中的作用。

Involvement of HIF-1alpha in UVB-induced epidermal hyperplasia.

机构信息

Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.

出版信息

Mol Cells. 2009 Dec 31;28(6):537-43. doi: 10.1007/s10059-009-0148-2. Epub 2009 Nov 19.

Abstract

Keratinocyte overgrowth after UVB exposure is believed to contribute to skin photoageing and cancer development. However, little is known about the transcription factors that epigenetically regulate keratinocyte response to UVB. Recently, HIF-1alpha was found to play a role in epidermal homeostasis by controlling the keratinocyte cell cycle, and thus, we hypothesized that HIF-1alpha is involved in UVB-induced keratinocyte growth. In cultured keratinocytes, HIF-1alpha was found to be down-regulated shortly after UVB exposure and to be involved in UVB-induced proliferation. In mice repeatedly treated with UVB, the epidermis became hyperplasic and keratinocytes lacked HIF-1alpha in nuclei. Based on these results, we suggest that the deregulation of HIF-1alpha is associated with UVB-induced hyperplasia of the epidermis. This work provides insight of the molecular mechanism underlying UV-induced photoageing and skin cancer development.

摘要

UVB 暴露后角质形成细胞的过度生长被认为是导致皮肤光老化和癌症发展的原因之一。然而,对于表观遗传调控角质形成细胞对 UVB 反应的转录因子知之甚少。最近发现,HIF-1α 通过控制角质形成细胞周期在表皮稳态中发挥作用,因此我们假设 HIF-1α 参与了 UVB 诱导的角质形成细胞生长。在培养的角质形成细胞中,发现 HIF-1α 在 UVB 暴露后不久即被下调,并参与了 UVB 诱导的增殖。在反复接受 UVB 处理的小鼠中,表皮出现增生,角质形成细胞核内缺乏 HIF-1α。基于这些结果,我们认为 HIF-1α 的失调与 UVB 诱导的表皮过度增生有关。这项工作为 UV 诱导的光老化和皮肤癌发展的分子机制提供了新的见解。

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