Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aim...Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis(P.gingivalis)in the development of BPH.Methods:The subgingival plaque(Sp)and prostatic fluid(Pf)of patients with BPH concurrent periodontitis were extracted and cultured for 16S r DNA sequencing.Ligature-induced periodontitis,testosterone-induced BPH and the composite models in rats were established.The P.gingivalis and its toxic factor P.gingivalis lipopolysaccharide(P.gLPS)were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate.P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.Results:P.gingivalis,Streptococcus oralis,Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis,and the average relative abundance of P.gingivalis was found to be the highest.P.gingivalis was detected in both Sp and Pf in 62.5%of patients.Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes.P.gingivalis and P.gLPS infection could induce obvious hyperplasia of the prostate epithelium and stroma(epithelial thickness was 2.97-fold and 3.08-fold that of control group,respectively),and increase of collagen fibrosis(3.81-fold and 5.02-fold that of control group,respectively).P.gingivalis infection promoted prostate cell proliferation,inhibited apoptosis,and upregulated the expression of inflammatory cytokines interleukin-6(IL-6;4.47-fold),interleukin-6 receptor-α(IL-6Rα;5.74-fold)and glycoprotein 130(gp130;4.47-fold)in prostatic tissue.P.g-LPS could significantly inhibit cell apoptosis,promote mitosis and proliferation of cells.P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex,which destroys the imbalance between proliferation and apoptosis of prostate cells,induces BPH.Conclusion:P.gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis.P.gingivalis infection can promote BPH,which may affect the progression of BPH via inflammation and the Akt signaling pathway.展开更多
Matrix metalloproteinase-9 (MMP-9) is a highly glycosylated endopeptidase implicated in a wide rage of oral mucosal inflammatory and neoplastic diseases, including chronic periodontitis, a persistent mucosal inflammat...Matrix metalloproteinase-9 (MMP-9) is a highly glycosylated endopeptidase implicated in a wide rage of oral mucosal inflammatory and neoplastic diseases, including chronic periodontitis, a persistent mucosal inflammation attributed primarily to infection by oral anaerobe, P. gingivalis. In this study, we explored the role of Rac1 and mitogen-activated protein kinases (MAPKs) in the processes of MMP-9 release in sublingual salivary gland cells exposed to P. gingivalis key endotoxin, cell wall lipopolysaccharide (LPS). We demonstrate that the LPS-elicited induction in the acinar cell MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>). Further, we reveal that the LPS-induced MMP-9 release involves ERK-mediated phosphorylation of cPLA<sub>2</sub> on Ser<sup>505</sup> that is essential for its membrane translocation with Rac1, and that this process requires p38 activation. Moreover, we show that phosphorylation and membrane localization of p38 with Rac1-GTP play a pivotal role in cPLA<sub>2</sub>-dependent induction in MMP-9 release. Thus collectively, our findings infer that P. gingivalis LPS-induced up-regulation in the acinar cell MMP-9 release requires ERK-dependent recruitment of cPLA<sub>2</sub> to the membrane localized Rac1/p38 complex.展开更多
基金supported(in part)by the National Natural Science Foundation of China(82200862,82370778)the Hubei Provincial Natural Science Foundation(2022CFB681,2023AFA061,2019CFB760)+4 种基金the Hubei Province Health and Family Planning Scientific Research Project(WJ2023M058,WJ2019H035)the Key Scientific Research Project of Education Department of Henan Province(22A320038)the Fundamental Research Funds for the Central Universities(2042023kf1019,2042023kf0051,2042022kf0072)the Zhongnan Hospital of Wuhan University,Science Technology and Innovation Seed Fund(CXPY2022074)the Young Top-notch Talent Cultivation Program of Hubei Province(for Prof.Zeng XT).
文摘Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly men.There is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains unclear.This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis(P.gingivalis)in the development of BPH.Methods:The subgingival plaque(Sp)and prostatic fluid(Pf)of patients with BPH concurrent periodontitis were extracted and cultured for 16S r DNA sequencing.Ligature-induced periodontitis,testosterone-induced BPH and the composite models in rats were established.The P.gingivalis and its toxic factor P.gingivalis lipopolysaccharide(P.gLPS)were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate.P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.Results:P.gingivalis,Streptococcus oralis,Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis,and the average relative abundance of P.gingivalis was found to be the highest.P.gingivalis was detected in both Sp and Pf in 62.5%of patients.Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes.P.gingivalis and P.gLPS infection could induce obvious hyperplasia of the prostate epithelium and stroma(epithelial thickness was 2.97-fold and 3.08-fold that of control group,respectively),and increase of collagen fibrosis(3.81-fold and 5.02-fold that of control group,respectively).P.gingivalis infection promoted prostate cell proliferation,inhibited apoptosis,and upregulated the expression of inflammatory cytokines interleukin-6(IL-6;4.47-fold),interleukin-6 receptor-α(IL-6Rα;5.74-fold)and glycoprotein 130(gp130;4.47-fold)in prostatic tissue.P.g-LPS could significantly inhibit cell apoptosis,promote mitosis and proliferation of cells.P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex,which destroys the imbalance between proliferation and apoptosis of prostate cells,induces BPH.Conclusion:P.gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis.P.gingivalis infection can promote BPH,which may affect the progression of BPH via inflammation and the Akt signaling pathway.
文摘Matrix metalloproteinase-9 (MMP-9) is a highly glycosylated endopeptidase implicated in a wide rage of oral mucosal inflammatory and neoplastic diseases, including chronic periodontitis, a persistent mucosal inflammation attributed primarily to infection by oral anaerobe, P. gingivalis. In this study, we explored the role of Rac1 and mitogen-activated protein kinases (MAPKs) in the processes of MMP-9 release in sublingual salivary gland cells exposed to P. gingivalis key endotoxin, cell wall lipopolysaccharide (LPS). We demonstrate that the LPS-elicited induction in the acinar cell MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>). Further, we reveal that the LPS-induced MMP-9 release involves ERK-mediated phosphorylation of cPLA<sub>2</sub> on Ser<sup>505</sup> that is essential for its membrane translocation with Rac1, and that this process requires p38 activation. Moreover, we show that phosphorylation and membrane localization of p38 with Rac1-GTP play a pivotal role in cPLA<sub>2</sub>-dependent induction in MMP-9 release. Thus collectively, our findings infer that P. gingivalis LPS-induced up-regulation in the acinar cell MMP-9 release requires ERK-dependent recruitment of cPLA<sub>2</sub> to the membrane localized Rac1/p38 complex.
