uman Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compound

Autor(es)

Bufalo, Michelle Cristiane ^{[1, 2]} ; de Almeida, Maira Estanislau Soares ^{[3, 2]} ; Jensen, Jose Ricardo ^[4] ; DeOcesano-Pereira, Carlos ^[2] ; Lichtenstein, Flavio ^[2] ; Picolo, Gisele ^[1] ; Chudzinski-Tavassi, Ana Marisa ^{[2, 5]} ; Sampaio, Sandra Coccuzzo ^{[3, 6]} ; Cury, Yara ^[1] ; Zambelli, Vanessa Olzon ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Butantan Inst, Lab Pain & Signaling, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Ctr Excellence New Target Discovery, BR-05503900 Sao Paulo - Brazil

^[3] Butantan Inst, Lab Pathophysiol, BR-05503900 Sao Paulo - Brazil

^[4] Butantan Inst, Immunogenet Lab, BR-05503900 Sao Paulo - Brazil

^[5] Butantan Inst, Innovat & Dev Ctr, Innovat & Dev Lab, BR-05503900 Sao Paulo - Brazil

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508220 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 11, n. 2 JAN 2022.
• Citações Web of Science: 0

Resumo

Increased collagen-derived advanced glycation end-products (AGEs) are consistently related to painful diseases, including osteoarthritis, diabetic neuropathy, and neurodegenerative disorders. We have recently developed a model combining a two-dimensional glycated extracellular matrix (ECM-GC) and primary dorsal root ganglion (DRG) that mimicked a pro-nociceptive microenvironment. However, culturing primary cells is still a challenge for large-scale screening studies. Here, we characterized a new model using ECM-GC as a stimulus for human sensory-like neurons differentiated from SH-SY5Y cell lines to screen for analgesic compounds. First, we confirmed that the differentiation process induces the expression of neuron markers (MAP2, RBFOX3 (NeuN), and TUBB3 (beta-III tubulin), as well as sensory neuron markers critical for pain sensation (TRPV1, SCN9A (Nav1.7), SCN10A (Nav1.8), and SCN11A (Nav1.9). Next, we showed that ECM-GC increased c-Fos expression in human sensory-like neurons, which is suggestive of neuronal activation. In addition, ECM-GC upregulated the expression of critical genes involved in pain, including SCN9A and TACR1. Of interest, ECM-GC induced substance P release, a neuropeptide widely involved in neuroinflammation and pain. Finally, morphine, the prototype opiate, decreased ECM-GC-induced substance P release. Together, our results suggest that we established a functional model that can be useful as a platform for screening candidates for the management of painful conditions. (AU)

• Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia