ZBTB16 exerts anti-angiogenic effects in rheumatoid arthritis by regulating HIF-1α pathway.

Abstract

Background: Rheumatoid arthritis (RA) is one complex chronic autoimmune disease, resulting body pain and badly affect the health of RA patients. Zinc finger and BTB domain containing 16 (ZBTB16) has been reported to participate into many diseases including osteoarthritis and osteoporosis.

Objective: To verify the regulatory functions of ZBTB16 in RA progression keep dimness.

Methods: The mRNA expressions were tested through RT-qPCR. The protein expressions were evaluated through western blot. The pathological changes of synovial tissues were determined through HE staining. The erosion and destruction of bone tissues were examined through safranin-O/fast green staining. The levels of TNF-α, IL-1β, IL-6 and MMP-3 were testified through ELISA. The fluorescence intensity of proteins was assessed through IF assay.

Results: Firstly, it was uncovered that ZBTB16 expression was markedly reduced in the synovium tissues of RA patients through analyzing GSE55235 expression profile by GEO2R online tool. Next, ZBTB16 expression was down-regulated in synovial tissues of RA patients. Moreover, ZBTB16 can alleviate the degree of paw swelling in CIA mice. ZBTB16 improved the pathological changes of synovial tissues in CIA mice. The levels of inflammatory factors and matrix metalloproteinase were increased in CIA mice, but these impacts were reversed after ZBTB16 amplification. ZBTB16 can relieve pannus in CIA mice. Besides, the triggered GRK2/HIF-1α pathway in CIA mice can be retarded after ZBTB16 overexpression.

Conclusion: ZBTB16 exerted anti-angiogenic effects in RA by blocking GRK2/HIF-1α pathway. This work hinted that ZBTB16 may be one useful target for RA treatment.