Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells
Publication in refereed journal


摘要Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.
著者Wei Hu, Lin Zhang, Ming Xing Li, Jing Shen, Xiao Dong Liu, Zhan Gang Xiao, Ding Lan Wu, Idy H. T. Ho, Justin C. Y. Wu, Cynthia K.Y. Cheung, Yu Chen Zhang, Alaster H. Y. Lau, Hassan Ashktorab, Duane T. Smoot, Fang Evandro F., Matthew T. V. Chan, Tony Gin, Wei Gong, William K. K. Wu, Chi Hin Cho
出版社Taylor & Francis: STM, Behavioural Science and Public Health Titles
頁次707 - 725
關鍵詞Helicobacter pylori, vitamin D3, Autophagy, Lysosome, PDIA3, Calcium

上次更新時間 2021-18-10 於 00:02