Versican in inflammation and tissue remodeling: The impact on lung disorders

Abstract

Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure comprises four different types of the core protein with attached glycosaminoglycans (GAGs) that can be sulfated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The GAGs that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican, it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies, our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease, and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor β driven, on-going remodeling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts, e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders.

Interplay of extracellular matrix and leukocytes in lung inflammation

“…Recent studies show that versican is expressed and accumulates in the lungs of mice in studies of gram-negative lung infection [59, 90], acute lung injury [93], allergen-induced airway inflammation [94], fibrosis [95], cancer [51, 55, 96, 97], and emphysema[98]. Similarly, in humans, versican accumulates in chronic lung diseases such as pulmonary fibrosis [99–101], acute respiratory distress syndrome [102, 103], asthma [104, 105], cancer [106], lymphangioleiomyomatosis [107], and chronic obstructive pulmonary disease (COPD) [108, 109]. Whereas numerous studies show that the re-expression and accumulation of versican is a common observation in lung disease, very little is known about the regulation of versican expression or the role of versican in the pathogenesis of lung disease.…”

iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma

“…Accumulation of versican could lead to increased stiffness in the lung thereby affecting lung function (43). Biglycan is sequestered in ECM under normal physiological conditions, and increase during tissue stress or injury thus inducing a wide range of effects.…”

Proteoglycans in normal physiology and carcinogenesis

“…Версикан участвует в регуляции клеточной адгезии, миграции и воспаления через взаимодействие его углеводных цепей ХС/ДС с цитокинами и факто-рами роста. Во время воспалительного ответа лейко-циты должны мигрировать из внутренних кровеносных сосудов в поврежденные окружающие ткани, при этом они сталкиваются с матриксом, сильно обогащенным версиканом, который, в свою очередь, способен вза-имодействовать со многими рецепторами на по-верхности иммунных клеток, включая CD44, P-селек-тин-гликопротеин-1 и Toll-подобные рецепторы [27]. В совокупности эти исследования показывают, что вер-сикан играет центральную роль в воспалении и в ре-зультате может рассматриваться как потенциальная терапевтическая мишень.…”