The adhesion protein of Mycoplasma genitalium inhibits urethral epithelial cell apoptosis through CypA-CD147 activating PI3K/ Akt/NF-κB pathway

The adhesion protein of Mycoplasma genitalium inhibits urethral epithelial cell apoptosis through CypA-CD147 activating PI3K/ Akt/NF-κB pathway
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生殖支原体粘附蛋白通过CypA-CD147激活PI3K/Akt/NF-κB通路抑制尿道上皮细胞凋亡

DOI:
10.1007/s00253-022-12146-z
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发表时间:
2022-09
影响因子:
5
通讯作者:
Zeng Y
Zeng Y
中科院分区:
工程技术2区
文献类型:
--
作者:
Liao Y;Peng K;Li X;Ye Y;Liu P;Zeng Y

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通过与宿主细胞膜上的受体相互作用,生殖支原体(一种主要通过性接触传播的原核细菌)可以粘附甚至进入细胞。生殖支原体 (MgPa) 的粘附蛋白在粘附和随后入侵宿主细胞中发挥着关键作用。我们前期的研究证实亲环素A(CypA)是人尿道上皮细胞(SV-HUC-1)膜上MgPa的受体,可以通过CypA-CD147-ERK-NF-κB途径诱导促炎细胞因子的产生。本研究旨在了解 MgPa 如何与其膜受体 CypA 相互作用从而引起宿主细胞凋亡。我们采用流式细胞术来观察 MgPa 是否可以预防或增强 SV-HUC-1 细胞的凋亡。使用蛋白质印迹法检测凋亡相关蛋白,例如 Bax、caspase-3 和 cleaved caspase-3。结果表明MgPa可以抑制SV-HUC-1细胞的凋亡。我们证明干扰CypA或CD147的表达可显着逆转MgPa对SV-HUC-1细胞凋亡的抑制作用,表明MgPa通过CypA/CD147抑制尿路上皮细胞凋亡。此外,我们发现MgPa通过CypA/CD147调节PI3K/Akt/NF-κB通路来抑制SV-HUC-1细胞凋亡。最终,通过Annexin V/PI实验验证了MgPa对CypA敲除小鼠尿路上皮细胞凋亡的抑制作用。结果证实MgPa还可以抑制小鼠尿路上皮细胞凋亡。综上所述,我们证明MgPa可以通过CypA/CD147调节PI3K/Akt/NF-κB通路来抑制SV-HUC-1细胞凋亡,为阐明生殖支原体在宿主细胞中的生存策略提供实验证据。要点: • 生殖支原体粘附蛋白通过 CypA-CD147 激活 PI3K/Akt/NF-κB 信号通路抑制人尿道上皮细胞凋亡 • 敲除 CypA 和 CD147 可以下调 SV-HUC-1 细胞中生殖支原体激活的 PI3K/Akt/NF-κB 通路 • MgPa 可以抑制正常尿道上皮细胞凋亡C57BL小鼠原代尿道上皮细胞,但不是CypA敲除的C57BL小鼠原代尿道上皮细胞。
By interacting with the receptor on the host cells membrane, Mycoplasma genitalium, a prokaryotic bacterium primarily transmitted through sexual contact, can adhere to and even enter cells. The adhesion protein of M. genitalium (MgPa) plays a critical function in the adhering and subsequent invasion into host cells. Our prior studies verified that cyclophilin A (CypA) was the receptor of MgPa on human urethral epithelial cells (SV-HUC-1) membrane and could induce pro-inflammatory cytokines production through the CypA-CD147-ERK-NF-κB pathway. This research aims to understand how MgPa interacts with its membrane receptor CypA to cause apoptosis in host cells. We employed flow cytometry to see if MgPa prevents or enhances apoptosis of SV-HUC-1 cells. The apoptosis-related proteins such as Bax, caspase-3, and cleaved caspase-3 were assayed using Western blot. Results suggested that MgPa could inhibit the apoptosis of SV-HUC-1 cells. And we demonstrated that interference with the expression of CypA or CD147 significantly reversed the inhibitory effect of MgPa on SV-HUC-1 cells apoptosis, indicating that MgPa inhibited urothelial cells apoptosis through CypA/CD147. Furthermore, we discovered that MgPa regulates the PI3K/Akt/NF-κB pathway through CypA/CD147 to inhibit SV-HUC-1 cells apoptosis. Ultimately, the inhibitory effect of MgPa on the apoptosis of the urothelial epithelial cells extracted from CypA-knockout mice was validated by Annexin V/PI assay. The results corroborated that MgPa could also inhibit mouse urothelial epithelial cells apoptosis. In summary, we demonstrated that MgPa could inhibit SV-HUC-1 cells apoptosis via regulating the PI3K/Akt/NF-κB pathway through CypA/CD147, providing experimental evidence for elucidating the survival strategies of M. genitalium in host cells. KEY POINTS: • M. genitalium protein of adhesion inhibited human urethral epithelial cells apoptosis through CypA-CD147 activating the signal pathway of PI3K/Akt/NF-κB • The knockdown of CypA and CD147 could downregulate the M. genitalium -activated PI3K/Akt/NF-κB pathway in SV-HUC-1 cells • MgPa could inhibit the apoptosis of normal C57BL mouse primary urethral epithelial cells, but not for CypA-knockout C57BL mouse primary urethral epithelial cells.
生殖支原体粘附蛋白通过亲环蛋白 A-CD147 激活人尿路上皮细胞中的 ERK-NF-κB 途径诱导炎症细胞因子
DOI: 10.3389/fimmu.2020.02052
发表时间: 2020
影响因子: 7.3
作者:
Li L;Luo D;Liao Y;Peng K;Zeng Y
通讯作者: Zeng Y
亲环蛋白 A:病原体感染的关键因素
DOI: 10.1007/s00253-021-11115-2
发表时间: 2021-03
影响因子: 5
作者:
Liao Y;Luo D;Peng K;Zeng Y
通讯作者: Zeng Y
DOI: 10.1590/1519-6984.228437
发表时间: 2021-12-01
影响因子: --
作者:
Obeng, E.
通讯作者: Obeng, E.
DOI: 10.1016/s0140-6736(81)92461-2
发表时间: 1981-06
期刊: The Lancet
影响因子: --
作者:
J. Tully;R. Cole;D. Taylor-Robinson;D. Rose
通讯作者: J. Tully;R. Cole;D. Taylor-Robinson;D. Rose
DOI: --
发表时间: 2005
期刊: Folia biologica
影响因子: 0.6
作者:
M. E. Kreft;S. Hudoklin;M. Sterle
通讯作者: M. E. Kreft;S. Hudoklin;M. Sterle