Human Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compounds.

Bufalo, Michelle Cristiane; Almeida, Maíra Estanislau Soares de; Jensen, José Ricardo; DeOcesano-Pereira, Carlos; Lichtenstein, Flavio; Picolo, Gisele; Chudzinski-Tavassi, Ana Marisa; Sampaio, Sandra Coccuzzo; Cury, Yara; Zambelli, Vanessa Olzon

Bufalo, Michelle Cristiane; Almeida, Maíra Estanislau Soares de; Jensen, José Ricardo; DeOcesano-Pereira, Carlos; Lichtenstein, Flavio; Picolo, Gisele; Chudzinski-Tavassi, Ana Marisa; Sampaio, Sandra Coccuzzo; Cury, Yara; Zambelli, Vanessa Olzon.

Afiliação

Bufalo MC; Laboratory of Pain and Signaling, Butantan Institute, São Paulo 05503-900, Brazil.
Almeida MES; Center of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil.
Jensen JR; Center of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil.
DeOcesano-Pereira C; Laboratory of Pathophysiology, Butantan Institute, São Paulo 05503-900, Brazil.
Lichtenstein F; Immunogenetics Laboratory, Butantan Institute, São Paulo 05503-900, Brazil.
Picolo G; Center of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil.
Chudzinski-Tavassi AM; Center of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil.
Sampaio SC; Laboratory of Pain and Signaling, Butantan Institute, São Paulo 05503-900, Brazil.
Cury Y; Center of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil.
Zambelli VO; Innovation and Development Laboratory, Innovation and Development Center, Butantan Institute, São Paulo 05503-900, Brazil.

Cells ; 11(2)2022 01 12.

Article em En | MEDLINE | ID: mdl-35053363

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 (ß-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.

Assuntos

Analgésicos/análise; Analgésicos/farmacologia; Colágeno/farmacologia; Avaliação Pré-Clínica de Medicamentos; Modelos Biológicos; Células Receptoras Sensoriais/citologia; Animais; Antígenos de Neoplasias/metabolismo; Biomarcadores/metabolismo; Diferenciação Celular/efeitos dos fármacos; Linhagem Celular Tumoral; Sobrevivência Celular/efeitos dos fármacos; Matriz Extracelular/metabolismo; Galectina 3/metabolismo; Regulação da Expressão Gênica/efeitos dos fármacos; Glicosilação/efeitos dos fármacos; Humanos; Proteínas Quinases Ativadas por Mitógeno/metabolismo; Canal de Sódio Disparado por Voltagem NAV1.7/genética; Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo; Neuritos/efeitos dos fármacos; Neuritos/metabolismo; Neurônios/citologia; Neurônios/efeitos dos fármacos; Proteínas Proto-Oncogênicas c-fos/metabolismo; Ratos; Receptores da Neurocinina-1/genética; Receptores da Neurocinina-1/metabolismo; Células Receptoras Sensoriais/efeitos dos fármacos; Células Receptoras Sensoriais/metabolismo; Substância P/metabolismo; beta-Endorfina/metabolismo

Palavras-chave

analgesic compounds; high-content screening; in vitro assays; inflammatory disease; nociception; two-dimensional culture

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Colágeno / Avaliação Pré-Clínica de Medicamentos / Analgésicos / Modelos Biológicos Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Animals / Humans Idioma: En Revista: Cells Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

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