Advanced glycation endproducts produced by in vitro glycation of type I collagen modulate the functional and secretory behavior of dorsal root ganglion cells cultivated in two-dimensional system

Autor(es)

Bufalo, Michelle C. ^[1] ; Almeida, Maira E. ^[2] ; Franca, Isabella Araujo ^[2] ; Zambelli, Vanessa O. ^[1] ; Sant'anna, Morena Brazil Martins ^[1] ; Kimura, Louise F. ^[1] ; Giardini, Aline Carolina ^[1] ; Cury, Yara ^[1] ; Sampaio, Sandra Coccuzzo ^{[3, 2]}

Afiliação do(s) autor(es)

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

^[2] Butantan Inst, Lab Pathophysiol, Av Vital Brazil 1500, BR-05503900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 382, n. 2-3 SEP 15 2019.
• Citações Web of Science: 0

Resumo

Advanced glycation end-products (AGEs) are proteins/lipids that are glycated upon sugar exposure and are often increased during inflammatory diseases such as osteoarthritis and neurodegenerative disorders. Here, we developed an extracellular matrix (ECM) using glycated type I collagen (ECM-GC), which produced similar levels of AGEs to those detected in the sera of arthritic mice. In order to determine whether AGEs were sufficient to stimulate sensory neurons, dorsal root ganglia (DRGs) cells were cultured on ECM-GC or ECM-NC-coated plates. ECM-GC or ECM-NC were favorable for DRG cells expansion. However, ECM-GC cultivated neurons displayed thinner F-actin filaments, rounded morphology, and reduced neuron interconnection compared to ECM-NC. In addition, ECM-GC did not affect RAGE expression levels in the neurons, although induced rapid p38, MAPK and ERK activation. Finally, ECM-GC stimulated the secretion of nitrite and TNF-alpha by DRG cells. Taken together, our in vitro glycated ECM model suitably mimics the in vivo microenvironment of inflammatory disorders and provides new insights into the role of ECM impairment as a nociceptive stimulus. (AU)

• Processo FAPESP: 16/12128-0 - Mecanismos moleculares da dor na artrite: identificação de novos alvos para o desenvolvimento de fármacos
• Beneficiário: Michelle Cristiane Búfalo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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: 12/51241-5 - Efeito da crotoxina sobre eventos fundamentais do processo angiogênico avaliado em matriz extracelular bidimensional e tridimensional: estudos in vitro
• Beneficiário: Sandra Coccuzzo Sampaio Vessoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/10886-4 - Ações de toxinas isoladas de diferentes venenos animais sobre a glicação de matriz extracelular no modelo de osteoartrite in vitro
• Beneficiário: Maíra Estanislau Soares de Almeida
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado