Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Life Sci. 2024 Nov 15;357:123083. doi: 10.1016/j.lfs.2024.123083. Epub 2024 Sep 27.
Ultraviolet (UV) B-induced damage in human epidermal keratinocytes (HEKs) initiates photocarcinogenesis. However, how diabetes influences photocarcinogenesis is not well understood. To investigate the impact of high-glucose environments on responses to UVB, we cultured HEKs in normal-glucose (NG) or high-glucose (HG) conditions (G6 and G26), followed by UVB irradiation at 25 mJ/cm (G6UVB and G26UVB). We performed next-generation sequencing and analyzed HEKs' expression profiles bioinformatically to identify candidate genes and cellular responses involved. We found UVB induced consistent responses in both NG- and HG-cultivated HEKs, but it also triggered certain distinct processes and pathways specifically in the HG groups. The 459 differentially expressed (DE) genes in the HG groups revealed their roles in chromatin remodeling, nucleosome assembly, and interferon signaling activation. Moreover, the 29 DE genes identified in G26UVB/G6UVB comparison, including the potent tumor suppressor gene TFPI2, were considered key genes contributing to HEKs' altered response to UVB in HG environments. UVB irradiation induced significantly higher TFPI2 expression in HG-cultivated HEKs than their NG-cultivated counterpart. Finally, HG-cultivation significantly increased oxidative stress, cyclobutane pyrimidine dimer formation, and apoptosis, while reducing HEKs' viability after UVB irradiation. These changes under HG conditions probably mediate cell fate toward death and tumor regression. Overall, our findings provide evidence and associated molecular basis on how HG conditions reduce keratinocytes' photocarcinogenic potential following UVB exposure.
紫外线 (UV) B 对人类表皮角质形成细胞 (HEKs) 的损伤引发光致癌作用。然而，糖尿病如何影响光致癌作用尚不清楚。为了研究高糖环境对 UVB 反应的影响，我们将 HEKs 在正常葡萄糖 (NG) 或高葡萄糖 (HG) 条件下 (G6 和 G26) 培养，然后用 25 mJ/cm 的 UVB 照射 (G6UVB 和 G26UVB)。我们进行了下一代测序，并对 HEKs 的表达谱进行了生物信息学分析，以鉴定涉及的候选基因和细胞反应。我们发现 UVB 在 NG 和 HG 培养的 HEKs 中均诱导了一致的反应，但它也在 HG 组中触发了某些特定的过程和途径。HG 组中 459 个差异表达 (DE) 基因揭示了它们在染色质重塑、核小体组装和干扰素信号激活中的作用。此外，在 G26UVB/G6UVB 比较中鉴定的 29 个 DE 基因，包括强大的肿瘤抑制基因 TFPI2，被认为是导致 HEKs 在 HG 环境中对 UVB 反应改变的关键基因。UVB 照射在 HG 培养的 HEKs 中诱导 TFPI2 表达显著高于 NG 培养的 HEKs。最后，HG 培养显著增加了氧化应激、环丁烷嘧啶二聚体形成和细胞凋亡，同时降低了 UVB 照射后 HEKs 的活力。HG 条件下的这些变化可能介导细胞命运向死亡和肿瘤消退。总的来说，我们的研究结果提供了证据和相关的分子基础，说明了 HG 条件如何降低角质形成细胞在暴露于 UVB 后的光致癌潜能。
