AUTHOR=Jia Xueting , Liu Jinan , He Yinxue , Huang Xiaofeng 

TITLE=Porphyromonas gingivalis secretion leads to dysplasia of normal esophageal epithelial cells via the Sonic hedgehog pathway

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.982636

DOI=10.3389/fcimb.2022.982636

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>To investigate the pathogenic effect of <italic>Porphyromonas gingivalis</italic> cultured media on the esophagus and the mechanism underlying the effect.</p></sec><sec><title>Background</title><p>Periodontitis is strongly associated with esophageal squamous cell carcinoma (ESCC). The cultured media of <italic>P. gingivalis</italic> may act on healthy esophagus to trigger a malignant transformation; however, this has not been confirmed.</p></sec><sec><title>Methods</title><p>Cell migration assays and cell cycle measurements were performed on normal human esophageal epithelial cells in the presence or absence of <italic>P. gingivalis</italic> cultured media. The esophagi of healthy adult C57BL/6J mice were isolated and cultured <italic>in-vitro</italic>. Hematoxylin-eosin and immunohistochemical staining using antibodies against proliferating cell nuclear antigen (PCNA), Claudin 1 and Claudin 4 were performed to detect dysplasia in specific tissues. Total mRNA was extracted to determine transcriptional dysregulation. A specific inhibitor of Sonic hedgehog signaling, cyclopamine, was used to confirm the underlying molecular mechanism.</p></sec><sec><title>Results</title><p>In the presence of <italic>P. gingivalis</italic> cultured media, proliferation and migration of normal human esophageal epithelial cells were up-regulated, and aneuploid cells appeared. Compared with control cells, the arrangement of mouse esophageal epithelial cells became disordered, the percentage of PCNA-positive cells increased, and the positive staining of Claudin 1 and Claudin 4 became weak. In addition, the expression of cancer-related pathway genes was up-regulated but tight junction-related gene expression was down-regulated. The Sonic hedgehog pathway was abnormally activated, and its inhibition reduced the pathogenic effect of <italic>P. gingivalis</italic> cultured media.</p></sec><sec><title>Conclusions</title><p>We revealed that the cultured media of the key periodontal pathogen, <italic>P. gingivalis</italic>, can induce the malignant transformation of normal esophageal epithelium through the Sonic hedgehog pathway.</p></sec>