Silica-induced fibrosis: an ancient response from the early metazoans

J Exp Biol. 2017 Nov 1;220(Pt 21):4007-4015. doi: 10.1242/jeb.166405.

Abstract

Exposure to crystalline silica particles causes silicosis, an occupational disease leading to an overproduction of collagen in the lung. The first step of this pathology is characterized by the release of inflammatory mediators. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine directly involved in silica-induced pulmonary fibrosis. The marine demosponge Chondrosia reniformis is able to incorporate silica grains and partially dissolve the crystalline forms apparently without toxic effects. In the present work, C. reniformis tissue explants were treated with fine quartz dust and the expression level of fibrogenic genes was assayed by qPCR, demonstrating an overexpression of a fibrillar and a non-fibrillar collagen and of prolyl-4-hydroxylase enzyme. The deposition of new collagen could also be documented in quartz-treated sponge explants. Furthermore, TNF pro-inflammatory cytokine overexpression and involvement in silica-induced sponge collagen biosynthesis was demonstrated in quartz-treated explants as compared with controls by means of specific TNF inhibitors affecting the fibrogenic gene response. As no documentable detrimental effect was observed in treated explants, we conclude that the C. reniformis unique quartz engulfment and erosion is physiological and beneficial to the animal, leading to new collagen synthesis and strengthening of the body stiffness. Thus, we put forward the hypothesis that an ancient physiological behaviour from the lowest of the Metazoa, persisting through evolution via the same molecular mediators such as TNF, may have become the cause of disease in the specialized tissues of higher animals such as mammals.

Keywords: Collagen; Evolution; Porifera; Silicosis; TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism
  • Porifera / metabolism*
  • Silicon Dioxide / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Silicon Dioxide
  • Collagen