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

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 is able to incorporate silica grains and partially dissolve the crystalline forms apparently without toxic effects. In the present work, 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 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.

Production, Characterization and Biocompatibility Evaluation of Collagen Membranes Derived from Marine Sponge Chondrosia reniformis Nardo, 1847

“…This again suggests that F2 may not be optimal for subsequent scaffolding procedures. Conversely, a low-diameter fibrillar organization was observable in F1, F3, and F4 PicroS staining, with the bigger collagen bundles that are typically present in C. reniformis native tissues [ 66 ] being completely removed during the first centrifugation steps.…”

Insights into the evolution of metazoan regenerative mechanisms: TGF superfamily member roles in tissue regeneration of the marine sponge Chondrosia reniformis Nardo, 1847

“…They were then synthesised by TibMolBiol (Genova, Italy). The primer sequences for GAPDH, fibrillar collagen and non-fibrillar collagen were reported in Pozzolini et al (2016a,b), while primers for proline-4 hydroxylase (P4H) and Bcl-2 were reported in Pozzolini et al (2017). The TGF1, TGF2, TGF3, TGF4, TGF5, TGF6, TGFR1, TGFR2, Piwi and Msi-1 primer sequences are presented in Table S1.…”

“…Newly synthesized tropocollagen in C. reniformis RTEs was assayed with a colorimetric method using the Sircol Assay (Biocolor Ltd, Carrickfergus, County Antrim, UK), as previously described (Pozzolini et al, 2017). The collagen content was then normalised to the weight of the wet tissue explants.…”

“…Indeed, C. reniformis tissue explants can be cultured in vitro (Nickel and Brümmer, 2003) or in aquaria (Pozzolini et al, 2012) to generate a large number of clones derived from the same specimen. Further studies identified various transcripts involved in fibrogenesis (Pozzolini et al, 2012(Pozzolini et al, , 2015(Pozzolini et al, , 2016a as well as in siliceous sediment management (Pozzolini et al, 2016b(Pozzolini et al, , 2017.…”

Identification, Purification and Molecular Characterization of Chondrosin, a New Protein with Anti-tumoral Activity from the Marine Sponge Chondrosia Reniformis Nardo 1847

“…The marine sponge Chondrosia reniformis Nardo 1847 is a common marine demosponge, widely distributed along all the Mediterranean Sea and East Atlantic Ocean, where it inhabits both shallow and deep-water environments [ 1 ]. This demosponge lacks siliceous spicules and its body is entirely formed by a dense collagenous matrix with peculiar molecular features [ 2 , 3 , 4 ] with finely-regulated production [ 5 ]. This sponge is also characterized by good regenerative properties [ 6 ] whose molecular mechanisms have recently been described [ 7 ].…”