Ziwei Wang, Yanhong Mao, Zihan Wang, Shuwei Li, Zhidan Hong, Rong Zhou, Shaoyuan Xu, Yao Xiong, Yuanzhen Zhang
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引用次数: 0
Abstract
Background: Histone lactylation is crucial in a variety of physiopathological processes, however, the function and mechanism of histone lactylation in endometriosis remain poorly understood. Therefore, the objective of this investigation was to illuminate the function and mechanism of histone lactylation in endometriosis. Methods: Immunohistochemistry was used to investigate the expression of histone lactylation. Cell Counting Kit-8 assay (CCK8), Transwell assay and endometriosis mouse models were used to investigate the effects of histone lactylation in vitro and in vivo. Transcriptomics and Immunoprecipitation-Mass Spectrometry (IP-MS), Western Blot, Co-Immunoprecipitation (Co-IP), quantitative reverse transcription polymerase chain reaction (qRT-PCR) and chromatin immunoprecipitation-qPCR (ChIP-qPCR) were used to explore the intrinsic mechanisms. Results: In this study, we found that histone lactylation was upregulated in endometriosis and could promote endometriosis progression both in vivo and in vitro. Mechanistically, histone lactylation H3K18la promoted the transcription of Ras homolog enriched in striatum (RASD2), and RASD2, in turn, increased the stability of CTP synthase 1 (CTPS1) by promoting the SUMOylation and inhibiting the ubiquitination of CTPS1, thereby promoting endometriosis progression. Conclusion: Overall, our findings indicated that histone lactylation could promote the progression of endometriosis through the RASD2/CTPS1 axis. This investigation uncovered a novel mechanism and identified prospective targets for endometriosis diagnosis and therapy.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.