The RNASET2 ribonuclease, belonging to the highly conserved RH/T2/s RNase gene family, has been recently shown to modulate inflammatory processes in both vertebrates and invertebrates. Indeed, the RNASET2 protein acts as a chemoattractor for macrophages in both in vitro and in vivo experimental settings and its expression significantly increases following bacterial infections. Moreover, we recently observed that injection of human recombinant RNASET2 protein in the body wall of the medicinal leech (a consolidated invertebrate model for both immune response and tissue regeneration) not only induced immune cell recruitment but also apparently triggered massive connective tissue remodelling as well. Based on these data, we evaluate here a possible role of leech recombinant RNASET2 protein (rHvRNASET2) in connective tissue remodelling by characterizing the cell types involved in this process through histochemical, morphological and immunofluorescent assays. Moreover, a time-course expression analysis of newly synthesized pro-collagen1α1 (COL1α1) and basic FGF receptor (bFGFR, a known fibroblast marker) following rHvRNASET2 injection in the leech body wall further supported the occurrence of rHvRNASET2-mediated matrix remodelling. Human MRC-5 fibroblast cells were also investigated in order to evaluate their pattern of collagen neosynthesis driven by rHvRNASET2 injection. Taken together, the data reported in this work provide compelling evidence in support of a pleiotropic role for RNASET2 in orchestrating an evolutionarily conserved crosstalk between inflammatory response and regenerative process, based on macrophage recruitment and fibroblast activation, coupled to a massive extracellular reorganization.

中文翻译：

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重组 HvRNASET2 蛋白在无脊椎动物模型中诱导显着的结缔组织重塑

RNASET2 核糖核酸酶属于高度保守的 RH/T2/s RNase 基因家族，最近已被证明可以调节脊椎动物和无脊椎动物的炎症过程。事实上，RNASET2 蛋白在体外和体内实验环境中都充当巨噬细胞的化学吸引器，其表达在细菌感染后显着增加。此外，我们最近观察到，在药用水蛭（一种用于免疫反应和组织再生的综合无脊椎动物模型）体壁中注射人重组 RNASET2 蛋白不仅诱导免疫细胞募集，而且显然还引发了大量的结缔组织重塑。根据这些数据，我们在此评估了水蛭重组 RNASET2 蛋白 (rHvRNASET2) 在结缔组织重塑中的可能作用，通过组织化学、形态学和免疫荧光分析表征该过程中涉及的细胞类型。此外，在水蛭体壁中注射 rHvRNASET2 后，对新合成的前胶原 1α1 (COL1α1) 和碱性 FGF 受体 (bFGFR，一种已知的成纤维细胞标记物) 的时程表达分析进一步支持了 rHvRNASET2 介导的基质重塑的发生。还研究了人 MRC-5 成纤维细胞，以评估它们由 rHvRNASET2 注射驱动的胶原新合成模式。综合起来，