Role of metalloproteinases and TNF-alpha in obesity-associated asthma in mice

Author(s)

Vieira, Cristiano Pedrozo ^[1] ; de Oliveira, Leticia Prado ^[2] ; Da Silva, Mariana Bombardi ^[2] ; Andre, Diana Majolli ^[1] ; Gandra Tavares, Edith Bastos ^[1] ; Pimentel, Edson Rosa ^[2] ; Antunes, Edson ^[1]

Affiliation

^[1] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, CP 6109, BR-13083863 Campinas, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 259, OCT 15 2020.
• Web of Science Citations: 0

Abstract

Numerous population studies conducted worldwide indicate that the prevalence of asthma is higher in obese versus lean individuals. It has been reported that sensitized lean mice has a better recovery of lung inflammation in asthma. Extracellular matrix (ECM) plays an essential role in the structural support of the lungs regulating the airways diameter, thus preventing its collapse during expiration. ECM renewal by metalloproteinase (MMPs) enzymes is critical for pulmonary biology. There seems to be an imbalance of MMPs activity in asthma and obesity, which can impair the lung remodeling process. In this study, we characterized the pulmonary ECM of obese and lean mice, non-sensitized and sensitized with ovalbumin (OVA). Pharmacological intervention was performed by using anti-TNF-alpha, and MMP-8 and MMP-9 inhibitors in obese and lean sensitized mice. Activity of MMPs was assessed by gelatinase electrophorese, western blotting and zymogram in situ. Unbalance of MMP-2, MMP-8, MMP-9 and MMP-12 was detected in lung tissue of OVA-sensitized obese mice, which was accompanied by high degradation, corroborating an excessive deposition of types I and III collagen in pulmonary matrix of obese animals. Inhibitions of TNF-alpha and MMP-9 reduced this MMP imbalance, clearly suggesting a positive effect on pulmonary ECM. Obese and lean mice presented diverse phenotype of asthma regarding the ECM compounds and the inhibition of MMPs pathway could be a good alternative to regulate the activity in ECM lungs of asthmatic obese individuals. (AU)

• FAPESP's process: 14/20640-7 - Characterization of the pulmonary extracellular matrix in the asthma associated obesity and study of inhibitors of metalloproteinases as a possible therapeutic target
• Grantee: Cristiano Pedrozo Vieira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral