title: Inhibition of pro-protein convertase subtilisin/kexin type 6 has a protective role against synovitis in a rat model of rheumatoid arthritis.
abstract: The aim of the present study was to assess the effects of pro-protein convertase subtilisin/kexin type 6 (PCSK6), a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of protein maturation, in fibroblast‑like synoviocytes (FLS) of a rat model of collagen‑induced arthritis (CIA). Cultured FLS from CIA models were subjected to small interfering RNA mediated PCSK6 knockdown, followed by assessment of the proliferation, invasive and migratory capacity, the secretion of inflammation factors and the cell cycle. Expression of genes associated with proliferation, invasion, migration and inflammation was detected by reverse transcription polymerase chain reaction. The results showed that PCSK6 knockdown significantly decreased the cell proliferation, invasion and migration of FLS from rats with CIA. ELISA showed an obvious decrease of tumor necrosis factor α and interleukin 1β secretion, and flow cytometric analysis revealed G0/G1 arrest of FLS following PCSK6 knockdown. Furthermore, a decrease in the mRNA levels of inflammation‑associated chemokine CXCL9, angiogenesis‑associated genes MMP‑2, MMP‑9 and NOSTRIN, hypoxia‑associated gene HIF‑1α, adhesion‑associated gene MPZL2, proliferation‑associated gene IGF‑2 and citrullination‑associated gene PADI4 was detected after PCSK6 knockdown. The results of the present study indicated that inhibition of PCSK6 may have a protective role against synovitis in rheumatoid arthritis.
authors.affiliation: Shandong Medicinal Biotechnology Centre, Jinan, Shandong 250022, P.R. China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Shandong Medicinal Biotechnology Centre, Jinan, Shandong 250022, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shandong Medicinal Biotechnology Centre, Jinan, Shandong 250022, P.R. China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Pan
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D008297:Male; D043484:Proprotein Convertases / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000067492:RNAi Therapeutics; D017208:Rats, Wistar; D013585:Synovitis / Q000150:complications* / Q000235:genetics* / Q000517:prevention & control
chemical_list: D034741:RNA, Small Interfering; C513087:Pcsk6 protein, rat; D043484:Proprotein Convertases