Abstract
Several studies have recently demonstrated that the correct regeneration of damaged tissues and the maintaining of homeostasis after wounds or injuries are tightly connected to different biological events, involving immune response, fibroplasia, and angiogenetic processes, in both vertebrates and invertebrates. In this context, our previous data demonstrated that the Hirudo verbana recombinant protein rHvRNASET2 not only plays a pivotal role in innate immune modulation, but is also able to activate resident fibroblasts leading to new collagen production, both in vivo and in vitro. Indeed, when injected in the leech body wall, which represents a consolidated invertebrate model for studying both immune response and tissue regeneration, HvRNASET2 induces macrophages recruitment, fibroplasia, and synthesis of new collagen. Based on this evidence, we evaluate the role of HvRNASET2 on muscle tissue regeneration and extracellular matrix (ECM) remodeling in rHvRNASET2-injected wounded leeches, compared to PBS-injected wounded leeches used as control. The results presented here not only confirms our previous evidence, reporting that HvRNASET2 leads to an increased collagen production, but also shows that an overexpression of this protein might influence the correct progress of muscle tissue regeneration. Moreover, due to its inhibitory effect on vasculogenesis and angiogenesis, HvRNASET2 apparently interfere with the recruitment of the myoendothelial vessel-associated precursor cells that in turn are responsible for muscle regeneration during wound healing repair.
Highlights
Correct tissue regeneration, following injuries or wounds, involves different biological processes, such as the scavenge of cellular debris and the activation of several processes such as vasculogenesis, angiogenesis, and stimulation/recruitment of immune cell progenitors
We have previously identified a plethora of cytokines and growth factors in injured leech tissues, such as VEGF, and FGFb, which support neovessel formation, immune/fibroblast cells recruitment, and proliferation and tissue remodeling by establishing a crosstalk between the innate immune response and tissue regeneration (Grimaldi et al, 2004; Tettamanti et al, 2004, 2005; Baranzini et al, 2020b)
Tissues were examined after 24, 48, 72 h, and 1 week from injuries, in order to evaluate the effect of HvRNASET2 on wound healing and tissue regeneration
Summary
Correct tissue regeneration, following injuries or wounds, involves different biological processes, such as the scavenge of cellular debris and the activation of several processes such as vasculogenesis, angiogenesis, and stimulation/recruitment of immune cell progenitors. Both in vertebrates and in invertebrates, the accurate coordination of these events is essential to re-establish the original, healthy tissue architecture (Pieper et al, 2002; de Eguileor et al, 2005; Li et al, 2005; Grimaldi et al, 2010). As already reported in vertebrates, the processes of vasculogenesis, angiogenesis, fibroplasia, and the activation and migration of immunocompetent/muscle precursors cells represent the main steps implicated in restoring damaged tissues in leeches as well (de Eguileor et al, 1999a, 2001; Tettamanti et al, 2005; Grimaldi et al, 2009)
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