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分泌卷曲相关蛋白 5(SFRP5)通过抑制 Wnt5a/JNK 通路保护 ATDC5 细胞免受 LPS 诱导的炎症和凋亡。

Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway.

机构信息

Department of Joint Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China.

Department of Clinical Medicine of Chinese and Western Medicine Integration, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

出版信息

J Orthop Surg Res. 2021 Feb 11;16(1):129. doi: 10.1186/s13018-021-02260-5.

Abstract

BACKGROUND

Secreted frizzled-related protein 5 (SFRP5) is an endogenous inhibitor of Wnt5a (wingless-type family member 5a), which has been implicated in anti-inflammatory response. In this study, we aimed to investigate whether SFRP5 could protect chondrocytes against LPS-induced inflammation and apoptosis.

METHODS

ATDC5 cells that overexpressed with SFRP5 or not were challenged with LPS to observe the effects of SFRP5 overexpression on LPS-triggered inflammation and apoptosis as well as Wnt5a/JNK activation. Wnt5a was elevated in ATDC5 cells in the presence of SFRP5 overexpression, to determine whether Wnt5a/JNK signaling was involved in the actions of SFRP5.

RESULTS

The mRNA and protein levels of SFRP5 was significantly reduced by LPS in a concentration-dependent manner. Overexpression of SFRP5 in ATDC5 cells inhibited LPS-induced inflammation and apoptosis, as evidenced by decreased production of TNF-α, IL-1β, IL-6, and ROS, together with a reduced ratio of TUNEL-positive cells, a lower expression of Bax and cleaved caspase 3, but a higher expression of Bcl-2. Meanwhile, SFRP5 overexpression also repress Wnt5a and phosphorylated JNK expression. However, the overexpression of Wnt5a considerably weakened the inhibitory effect of SFRP5 on LPS-triggered inflammation and apoptosis. Besides, the level of Wnt5a and JNK phosphorylation, which was inhibited by SFRP5 overexpression, was also partially recovered by Wnt5a overexpression.

CONCLUSION

SFRP5 could alleviate LPS-induced ATDC5 cell inflammation and apoptosis; these actions may rely on repressing Wnt5a/JNK activation.

摘要

背景

分泌型卷曲相关蛋白 5(SFRP5)是 Wnt5a(无翅型家族成员 5a)的内源性抑制剂,它与抗炎反应有关。在这项研究中,我们旨在研究 SFRP5 是否可以保护软骨细胞免受 LPS 诱导的炎症和凋亡。

方法

用 SFRP5 过表达或未过表达的 ATDC5 细胞进行 LPS 刺激,观察 SFRP5 过表达对 LPS 触发的炎症和凋亡以及 Wnt5a/JNK 激活的影响。在 SFRP5 过表达的情况下,升高 ATDC5 细胞中的 Wnt5a,以确定 Wnt5a/JNK 信号是否参与 SFRP5 的作用。

结果

LPS 以浓度依赖性方式显著降低 ATDC5 细胞中 SFRP5 的 mRNA 和蛋白水平。在 ATDC5 细胞中过表达 SFRP5 可抑制 LPS 诱导的炎症和凋亡,表现在 TNF-α、IL-1β、IL-6 和 ROS 的产生减少,TUNEL 阳性细胞的比例降低,Bax 和 cleaved caspase 3 的表达降低,Bcl-2 的表达升高。同时,SFRP5 过表达还抑制了 Wnt5a 和磷酸化 JNK 的表达。然而,Wnt5a 的过表达大大削弱了 SFRP5 对 LPS 触发的炎症和凋亡的抑制作用。此外,SFRP5 过表达抑制的 Wnt5a 和 JNK 磷酸化水平也部分被 Wnt5a 过表达所恢复。

结论

SFRP5 可减轻 LPS 诱导的 ATDC5 细胞炎症和凋亡;这些作用可能依赖于抑制 Wnt5a/JNK 的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2925/7877043/7bd6f9b073ec/13018_2021_2260_Fig1_HTML.jpg

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