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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Experimental Cell Research; v. 382, n. 2-3 SEP 15 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/12128-0 - Pain in arthritis molecular mechanisms: identification of new targets for drug development
• Grantee: Michelle Cristiane Búfalo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 12/51241-5 - Effect of Crotoxin on several steps in angiogenese evaluated in two dimensional and three dimensional matrices: in vitro studies
• Grantee: Sandra Coccuzzo Sampaio Vessoni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/10886-4 - Toxins isolated from animal venoms acting on glycation of in vitro osteoarthritis model extracellular matrix
• Grantee: Maíra Estanislau Soares de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral