长波紫外线UVA损伤机体同时诱导保护性作用分子，但目前尚无突破性发现。UVA照射人体皮肤成纤维细胞FBs诱导血红素氧合酶1(HO-1) 的高表达，与Nrf2及Bach1分别呈正、负相关。我们发现UVA激活翻译起始因子eIF2α,但eIF2α是否参与转录因子Nrf2及Bach1调控HO-1从而对皮肤应激、内环境的稳态起保护作用未知。我们假定eIF2α及下游分子加入Nrf2及Bach1通路调节HO-1表达。本项目拟使用FBs，研究eIF2α及下游分子参与Nrf2及Bach1 调控UVA诱导HO-1表达的机制，明确该通路对UVA所致细胞生物学行为的作用以及动物光老化的影响；阐明eIF2α/Nrf2及Bach1 动态调节HO-1表达的保护作用，为抵御UVA照射皮肤损伤、抗光老化及临床光治疗提供理论基础。

Ultraviolet A (UVA, 320-400 nm) irradiation causes significant oxidative stress to human skin, leads to inflammation, photoaging, and contributes to skin cancer. UVA also leads to the strong up-regulation of heme oxygenase-1 (HO-1) expression in human dermal skin fibroblasts (FBs) and activates eIF2α(eukaryotic translation initiation factor 2 alpha). Both HO-1 induction and eIF2α activation are cellular response to oxidative stress. It is not clear if eIF2α and downstream factors join with transcription factor Nrf2 (Nuclear factor -erythroid (NF-E2)-related factor2) and Bach1 (BTB and CNC-homology 1) to mediate the induction of HO-1 by UVA irradiation, therefore protect skin against UVA-induced damage,thus contributes to the restoration of cellular redox homeostasis. We've found that the UVA-induced HO-1 levels is correlated with Nrf2 and Bach1 and modulate Nrf2 or Bach1 levels may alter cellular response to UVA irradiation. We hypothesize that eIF2α pathway joins with Nrf2, antagonist with Bach1 to regulate HO-1 expression. We aim to identify eIF2α via downstream activate transcription factor (ATF3 and ATF4), together with Nrf2, to balance with suppressor Bach1 to modulate HO-1 expression. In this study, the biological effects of eIF2α/Nrf2 and Bach1 -HO-1 pathway on UVA induced damage in vitro in FBs as well as in vivo in mice skin will be illustrated. This study may offer guidance to the reduction of photoaging, photodamage as well as effectively using of phototherapy.