Fibroblastic SMOC2 Suppresses Mechanical Nociception by Inhibiting Coupled Activation of Primary Sensory Neurons

• DOI: 10.1523/jneurosci.2132-21.2022
• Publication Date: 2022-04-18T17:50:16Z
• Authors: Shuo Zhang; Bing Cai; Zhen Li; Kaikai Wang; Lan Bao; Changlin Li; Xu Zhang
• Keywords: Inflammation; Male; Nociception; 0301 basic medicine; Sensory Receptor Cells; Calcium-Binding Proteins; Fibroblasts; Mice; 03 medical and health sciences; HEK293 Cells; Ganglia, Spinal; Animals; Humans; Female; Receptors, Purinergic P2X7

Nociceptive information is detected and transmitted by neurons in the DRG. Recently, single-cell RNA sequencing has revealed molecular profile of various cell types, including fibroblasts However, role molecules needs to be elucidated nociceptive regulation. Here, we found that secreted modular calcium-binding protein 2 (SMOC2) was become a component basement membrane envelop unit consisting DRG attached satellite glial cells. KO Smoc2 both sexes mice led increased neuronal clusters decreased mechanical threshold, but unchanged noxious thermal response. Knockdown phenocopied behavioral performance mice. In vivo calcium imaging showed coupled activation adjacent induced stimuli, which reversed injection SMOC2. Importantly, SMOC2 interacted with P2X7 receptor (P2X7R) suppressed ATP-induced HEK293 cells expressing this receptor. Injection A740003, an antagonist P2X7R, reduced stimuli did not further enhance SMOC2-inhibited effect. Furthermore, peripheral inflammation resulted clusters. inhibited coupling from inflammation. This study reveals specific fibroblastic suppressing nociception through inhibiting communication neurons, provides important mechanism SIGNIFICANCE STATEMENT The function rarely noticed regulation sensation. reveal surrounded neuron required for maintaining basal threshold Loss leads stimuli. Peripheral causes fibroblast SMOC2, may result increase neurons. Mechanistically, interacts suppresses inhibit