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LOX/LOXL in pulmonary fibrosis: potential therapeutic targets
Published in Journal of Drug Targeting, 2019
Lijun Chen, Shifeng Li, Wande Li
LOX may be the best-studied isoform to date and was the first to get cloned [12]. It is synthesised by fibrogenic cells such as fibroblasts and vascular smooth muscle cells as a 46kDa preproenzyme with N-terminal signal sequences that direct nascent proteins into the lumen of the rough endoplasmic reticulum. The proprotein resulting from cleavage of the N-terminal signal peptide undergoes N-linked glycosylation in the endoplasmic reticulum and Golgi apparatus, and is then extracellularly secreted through secretory vesicles as a 50kDa proenzyme. In the extracellular matrix (ECM), the 50kDa proLOX is further processed by proteolysis into the enzymatically active 32kDa mature species and the LOX propeptide (LOX-PP) [13]. Procollagen C-proteinases were shown to be responsible for the extracellular proteolytic processing of prolysyl oxidase to form active LOX and release the LOX-PP [14]. Active LOX and LOX-PP each have independent biological functions.