β1,4-galactosyltransferase-I in synovial tissue of collagen-induced rat model of rheumatoid arthritis

Abstract

β1,4-galactosyltransferase-I (β1,4-GalT-I), which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of selectin ligands such as sialyl Lewis (sLe(x)) and sulfated sLe(x). Previous studies showed that inflammatory responses of β1,4-GalT-I-deficient mice were impaired because of the defect in selectin-ligand biosynthesis. However, the expression of β1,4-GalT-I and its biological function in rheumatoid arthritis (RA) remain to be elucidated. The mRNA and protein expression of β1,4-GalT-I increased in synovial tissue of the RA group compared with the Normal group at 10d and 15d after collagen-induced. Double staining indicated β1,4-GalT-I overlapped with macrophage-like synoviocytes (MLSs), fibroblast-like synoviocytes (FLSs), neutrophils and tumor necrosis factor-α (TNF-α). Moreover, β1,4-GalT-I mRNA in FLSs in vitro was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that expression of TNF-α was attenuated in FLSs in vitro treated with β1,4-GalT-I-Ab. We therefore suggest that β1,4-GalT-I may play an important role in the inflammation process of RA synovial tissue, which would provide the foundation for further researching into the concrete mechanism of β1,4-GalT-I in RA.

Elevated Expression of β1,4-Galactosyltransferase-I in Cartilage and Synovial Tissue of Patients with Osteoarthritis

“…We had previously reported, for the first time, that β1,4-GalT-I may play an important role in the inflammatory processes in synovial tissue of patients [18,19] and in a collagen-induced rat model of RA [20]. In the present study, we investigated the expression of β1,4-GalT-I in the cartilage and synovial tissue of patients with OA and explored the mechanism involved in OA pathogenesis.…”

“…It has shown reduced inflammatory responses [16] and delayed skin wound healing attributable to impaired leukocyte infiltration caused by the decreased biosynthesis of selectin ligands in mice deficient in β1,4-GalT-I [17]. We had previously reported, for the first time, that β1,4-GalT-I may play an important role in the inflammatory processes in synovial tissue of patients [18,19] and in a collageninduced rat model of rheumatoid arthritis (RA) [20]. In the present study, we investigated the expression of β1,4-GalT-I in the cartilage and synovial tissue of patients with OA, then explored the mechanism involved in OA pathogenesis.…”

MicroRNA-15a/β1,4-GalT-I axis contributes to cartilage degeneration via NF-κB signaling in osteoarthritis

“…Furthermore, in a surgically induced OA model, the expression of β1,4-GalT-I was found to be increased on the first day after the operation. 9 These findings suggest that β1,4-GalT-I plays a crucial role in the development and progression of inflammation in the synovial tissue associated with OA.…”

“…In articular cartilage of microsurgery-induced acute injurious OA, miR-15a was low expressed and β1,4-GalT-I were high. 9 At this point, miR-15a protected chondrocytes from inflammation-induced senescence and damage, whereas β1,4-GalT-I instead promoted chondrocyte senescence and inflammatory responses. When OA progresses to the chronic inflammatory (Grade III‒IV) stage, miR-15a promotes the degeneration of chondrocytes by inhibiting parathyroid hormone-related protein.…”

“… 6 By decreasing Toll-Like Receptor 4 (TLR4) signaling and p65 and IKK phosphorylation, β1,4-GalT-I has also been demonstrated to diminish joint inflammation and prevent chondrocyte apoptosis in OA. 7 According to previous research, 8 β1,4-GalT-I is significantly elevated in the synovial tissue of rheumatoid arthritis patients, which is involved in the inflammatory response of synovial tissue. Furthermore, in a surgically induced OA model, the expression of β1,4-GalT-I was found to be increased on the first day after the operation.…”