Contribution of membrane raft redox signalling to visfatin-induced inflammasome activation and podocyte injury.
Contribution of membrane raft redox signalling to visfatin-induced inflammasome activation and podocyte injury.
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DOI：
10.18632/aging.205243
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发表时间：
2023-11-17
期刊：
影响因子：
5.2
通讯作者：
Boini, Krishna M.
中科院分区：
文献类型：
--
作者：
Koka, Saisudha;Surineni, Sreenidhi;Singh, Gurinder Bir;Boini, Krishna M.
最近我们发现脂肪因子内脂素诱导的 NLRP3 炎性体激活有助于足细胞损伤。然而，visfatin如何诱导Nlrp3炎症小体激活和足细胞损伤的分子机制仍不清楚。本研究测试了膜筏（MR）氧化还原信号通路是否在内脂素诱导的足细胞中NLRP3炎症小体的形成和激活中发挥核心作用。内脂素刺激后，在膜筏 (MR) 簇中观察到 NADPH 氧化酶亚基 gp91phox 和 p47phox 的聚集，在足细胞中形成 MR 氧化还原信号平台。该信号平台的形成被 MR 干扰剂 MCD 或 NADPH 氧化酶抑制剂 DPI 预先治疗所阻断。此外，与对照细胞相比，内脂素刺激显着增加了 Nlrp3 与 Asc 或 Nlrp3 与 caspase-1 的共定位、IL-β 的产生、足细胞的细胞通透性。 MCD、DPI、WEHD 预处理显着消除了内脂素诱导的 NLRP3 与 Asc 或 NLRP3 与 caspase-1、IL-1β 产生和足细胞细胞通透性的共定位。此外，免疫荧光分析表明，visfatin 治疗显着降低了 podocin 和 nephrin 的表达（足细胞损伤），并且之前用 DPI、WEHD、MCD 治疗减弱了 visfatin 诱导的 podocin 和 nephrin 的减少。总之，我们的结果表明，内脂素通过 NADPH 氧化酶亚基的聚集和激活，刺激足细胞膜中的膜筏聚集，形成氧化还原信号平台，增强 O2·− 的产生，并导致足细胞中 NLRP3 炎性体激活，最终导致足细胞损伤。
Recently we have shown that adipokine visfatin-induced NLRP3 inflammasome activation contributes to podocyte injury. However, the molecular mechanisms of how visfatin-induces the Nlrp3 inflammasome activation and podocyte damage is still unknown. The present study tested whether membrane raft (MR) redox signalling pathway plays a central role in visfatin-induced NLRP3 inflammasomes formation and activation in podocytes. Upon visfatin stimulation an aggregation of NADPH oxidase subunits, gp91phox and p47phox was observed in the membrane raft (MR) clusters, forming a MR redox signalling platform in podocytes. The formation of this signalling platform was blocked by prior treatment with MR disruptor MCD or NADPH oxidase inhibitor DPI. In addition, visfatin stimulation significantly increased the colocalization of Nlrp3 with Asc or Nlrp3 with caspase-1, IL-β production, cell permeability in podocytes compared to control cells. Pretreatment with MCD, DPI, WEHD significantly abolished the visfatin-induced colocalization of NLRP3 with Asc or NLRP3 with caspase-1, IL-1β production and cell permeability in podocytes. Furthermore, Immunofluorescence analysis demonstrated that visfatin treatment significantly decreased the podocin and nephrin expression (podocyte damage) and prior treatments with DPI, WEHD, MCD attenuated this visfatin-induced podocin and nephrin reduction. In conclusion, our results suggest that visfatin stimulates membrane raft clustering in the membrane of podocytes to form redox signaling platforms by aggregation and activation of NADPH oxidase subunits enhancing O2·− production and leading to NLRP3 inflammasome activation in podocytes and ultimate podocyte injury.
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影响因子：
3.7
作者：
Rajamäki K;Lappalainen J;Oörni K;Välimäki E;Matikainen S;Kovanen PT;Eklund KK
通讯作者：
Eklund KK
DOI：
10.1159/000484623
发表时间：
2017
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Boini KM;Hussain T;Li PL;Koka S
通讯作者：
Koka S
影响因子：
4.8
作者：
Bernhard, D;Csordas, A;Wick, G
通讯作者：
Wick, G
影响因子：
2.5
作者：
Eyileten, Tayfun;Sonmez, Alper;Yilmaz, Mahmut Ilker
通讯作者：
Yilmaz, Mahmut Ilker
影响因子：
5.6
作者：
Singh, Gurinder Bir;Zhang, Yang;Koka, Saisudha
通讯作者：
Koka, Saisudha