Inhibiting ABCC4 for rheumatoid arthritis

Inhibiting the cAMP efflux transporter ABCC4 in synovial fibroblasts expressing the coagulation factor CD142 could help treat rheumatoid arthritis by promoting intracellular cAMP accumulation and signaling, which decreases expression of genes that promote synovial fibroblast migration into the joints to drive meniscal injury.

In rheumatoid arthritis patients requiring total knee arthroplasty, CD142⁺ synovial fibroblasts were highly expressed in meniscal cells. The CD142⁺ synovial fibroblast numbers were higher in knee synovium tissue and fluid samples from rheumatoid arthritis patients than in those from osteoarthritis patients and other individuals without rheumatoid arthritis. Among rheumatoid arthritis patients with long-term knee symptoms, CD142⁺ synovial fibroblast numbers were higher in the synovial lining layer that produces synovial fluid from patients that underwent total knee arthroplasty than in the same tissue from patients that did not undergo total knee arthroplasty. ...