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HSF1 dependent autophagy activation contributes to the survival of melanocytes under oxidative stress in vitiligo

Published:November 12, 2021DOI:


      Autophagy plays a protective role in the oxidative stress-induced melanocyte death. Dysregulated autophagy increases the sensitivity of melanocytes in response to oxidative damage and promotes the melanocyte degeneration in vitiligo. However, the molecular mechanism underlying this process is not fully understood. Here, using RNA-Seq technology, we compared the transcriptome change between normal and vitiligo melanocytes with or without treatment of oxidative stress. We found that autophagy-related protein 5 and 12 (Atg5 and Atg12), the critical components for autophagosome formation, were significantly reduced in vitiligo melanocytes under oxidative stress. Mechanistically, heat shock factor 1 (HSF1) is the prime transcription factor for both Atg5 and Atg12, accounting for the reduced level of Atg5 and Atg12 in vitiligo melanocytes. Deficiency of HSF1 led to accumulation of intracellular reactive oxygen species (ROS), imbalance of mitochondrion membrane potential and apoptosis in melanocytes exposure to oxidative stress. Further, overexpression of HSF1 could ameliorate oxidative stress-induced melanocytes death by activation of autophagy through upregulating Atg5 and Atg12. These findings suggested targeting HSF1-Atg5/12 axis could prevent oxidative stress-induced melanocyte death and may be used as therapeutic strategies for vitiligo treatment.

      Key words

      Abbreviations used:

      Atg5 (autophagy-related protein 5), Atg12 (autophagy-related protein 12), HSF1 (heat shock factor 1), Atg7 (autophagy-related protein 7), GATA4 (GATA Binding Protein 4), ATG9B (autophagy-related protein 9B), HSPs (heat shock proteins), qRT-PCR (quantitative real-time PCR), PIG3V (vitiligo melanocyte cell line), PIG1 (normal human melanocyte cell line), DEGs (differentially expressed genes), Baf-A1 (Bafilomycin A1)
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