SPOCK2 Modulates Neuropathic Pain by Interacting with MT1-MMP to Regulate Astrocytic MMP-2 Activation in Rats with Chronic Constriction Injury

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2024 Feb 22

PMID 38388415

Authors

Chenglong Wang

Yitong Xu

Miao Xu

Cong Sun

Xiaojiao Zhang

Xueshu Tao

Tao Song

Affiliations

Soon will be listed here.

Abstract

Background: Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI).

Methods: Sprague-Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein-protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments.

Results: We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1β production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain.

Conclusions: Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1β production to achieve positive promotion of NP.

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