Rheumatology: HOXA5 is a key regulator of the expression of 3 types of signaling proteins in the synovial membrane of rheumatoid arthritis patients

Objective: Decreased 3 types of signaling proteins in synovial tissue of patients with rheumatoid arthritis (RA), which are involved in the pathogenesis
of the disease.
The purpose of this study is to identify transcription factors
involved in the expression of 3 types of signaling proteins in the synovial membrane of RA patients.

Methods: Protein and mRNA expression
in synovial tissue, human umbilical vein endothelial cells (HUVECs) and RA fibroblast-like synovial cells (FLS) were detected by ELISA, western blotting and qPCR.
Expression of TCF-3, EBF-1, and HOXA5 was knocked out using siRNA
.
Cell viability, migration, and invasion were measured by MTT, calcein, wound closure, and invasion
assays, respectively.

Results: Compared with IAR patients, mRNA expression of all 3 types of signaling proteins in the synovial membrane of RA was significantly reduced
.
Computer analysis showed that TCF-3, EBF-1, and HOXA5 are transcription factors involved in the expression of these signaling proteins.

The silencing of TCF-3, EBF-1, and HOXA5 significantly reduced the expression
of several class 3 signaling protein members in FLS and HUVEC.

Importantly, the expression of HOXA5 in the synovial membrane of RA was significantly reduced compared to patients with IAR and was inversely correlated
with clinical disease parameters.
In addition, TNF-α downregulated the expression
of HOXA5 in FLS and HUVEC.
Finally, HOXA5 silencing enhances the migration and invasion capabilities of FLS and the survivability
of HUVEC.

Conclusion: HOXA5 expression decreases during RA progression, which may be a novel therapeutic strategy to regulate synovial hyperplasia by regulating the expression of 3 types of signaling proteins.

Sources:

Martínez-Ramos S, Rafael-Vidal C, Malvar-Fernández B, et al.
HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients [published online ahead of print, 2022 Nov 18].
Rheumatology (Oxford).
2022; keac654.
doi:10.
1093/rheumatology/keac654.