The correct balance between collagen synthesis and degradation is essential for almost every aspect of life, from development to healthy aging, reproduction and wound healing. When this balance is compromised by external or internal stress signals, it very often leads to disease as is the case in fibrotic conditions. Fibrosis occurs in the context of defective tissue repair and is characterized by the excessive, aberrant and debilitating deposition of fibril-forming collagens. Therefore, the numerous proteins involved in the biosynthesis of fibrillar collagens represent a potential and still underexploited source of therapeutic targets to prevent fibrosis. One such target is procollagen C-proteinase enhancer-1 (PCPE-1) which has the unique ability to accelerate procollagen maturation by BMP-1/tolloid-like proteinases (BTPs) and contributes to trigger collagen fibrillogenesis, without interfering with other BTP functions or the activities of other extracellular metalloproteinases. This role is achieved through a fine-tuned mechanism of action that is close to being elucidated and offers promising perspectives for drug design. Finally, the in vivo data accumulated in recent years also confirm that PCPE-1 overexpression is a general feature and early marker of fibrosis. In this review, we describe the results which presently support the driving role of PCPE-1 in fibrosis and discuss the questions that remain to be solved to validate its use as a biomarker or therapeutic target.
Keywords: ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; AS, aortic valve stenosis; BMP, bone morphogenetic protein; Biomarker; CKD, chronic kidney disease; CP, C-propeptide; CUB, complement, Uegf, BMP-1; CVD, cardiovascular disease; Collagen; DMD, Duchenne muscular dystrophy; ECM, extracellular matrix; EGF, epidermal growth factor; ELISA, enzyme-linked immunosorbent assay; Fibrillogenesis; Fibrosis; HDL, high-density lipoprotein; HSC, hepatic stellate cell; HTS, hypertrophic scar; IPF, idiopathic pulmonary fibrosis; LDL, low-density lipoprotein; MI, myocardial infarction; MMP, matrix metalloproteinase; NASH, nonalcoholic steatohepatitis; NTR, netrin; OPMD, oculopharyngeal muscular dystrophy; PABPN1, poly(A)-binding protein nuclear 1; PCP, procollagen C-proteinase; PCPE, procollagen C-proteinase enhancer; PNP, procollagen N-proteinase; Proteolysis; SPC, subtilisin proprotein convertase; TGF-β, transforming growth-factor β; TIMP, tissue inhibitor of metalloproteinases; TSPN, thrombospondin-like N-terminal; Therapeutic target; eGFR, estimated glomerular filtration rate; mTLD, mammalian tolloid; mTLL, mammalian tolloid-like.
© 2021 The Author(s).