HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury.

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.

Live-cell imaging-based dynamic vascular formation assay for antivascular drug evaluation and screening.

New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. However, most existing methods for evaluating cell vascular formation are limited to static analysis and prone to bias due to time, field of vision, and parameter selection. Code scripts, such as AngiogenesisAnalyzer.ijm, AutomaticMeasure.ijm, and VM.R., were developed to study the dynamic angiogenesis process. This method was used to screen drugs that could affect the time, maximum value, tilt, and decline rate of cell vascular formation and angiogenesis. Animal experiments have confirmed that these drugs could inhibit the formation of blood vessels. This work provides a new perspective for the research of angiogenesis process and is helpful to the development of drugs related to angiogenesis.