Anti-RBP4 monoclonal antibody, clone RB48

Serum retinol-binding protein 4 (RBP4) is the sole specific transport protein for retinol in the blood, but it is also an adipokine with retinol-independent, proinflammatory activity associated with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Moreover, two separate studies reported that patients with proliferative diabetic retinopathy have increased serum RBP4 levels compared to patients with mild or no retinopathy, yet the effect of increased levels of RBP4 on the retina has not been studied. Here we show that transgenic mice overexpressing RBP4 (RBP4-Tg mice) develop progressive retinal degeneration, characterized by photoreceptor ribbon synapse deficiency and subsequent bipolar cell loss. Ocular retinoid and bisretinoid levels are normal in RBP4-Tg mice, demonstrating that a retinoid-independent mechanism underlies retinal degeneration. Increased expression of pro-interleukin-18 (pro-IL-18) mRNA and activated IL-18 protein and early-onset microglia activation in the retina suggest that retinal degeneration is driven by a proinflammatory mechanism. Neither chronic systemic metabolic disease nor other retinal insults are required for RBP4 elevation to promote retinal neurodegeneration, since RBP4-Tg mice do not have coincident retinal vascular pathology, obesity, dyslipidemia, or hyperglycemia. These findings suggest that elevation of serum RBP4 levels could be a risk factor for retinal damage and vision loss in nondiabetic as well as diabetic patients.

Craniosynostosis is one of the most common congenital craniofacial deformities and could cause a series of diseases or defects. But the molecular mechanism underlying craniosynostosis is rarely reported. Retinal-binding protein 4 (RBP4) was shown to be involved in osteogenesis and decreased dramatically in prematurely fused suture. To investigate the role of RBP4 in osteogenesis, a cell line stably expressing RBP4 was constructed based on MC3T3-E1 cells and RBP4 overexpression was confirmed at both mRNA level and protein level. Then we found that RBP4 upregulation promoted proliferation of MC3T3-E1 cell and significantly increased alkaline phosphatase activity from day 7 to day 14 in MC3T3-E1 cells. Further, in alizarin red staining assay, RBP4 was shown to increase the deposit of calcium phosphate remarkably from day 14 to day 21 in MC3T3-E1 cells cultured in differentiated medium. This indicated that RBP4 prompted the mineralization of MC3T3-E1 cells. In accordance with this phenotype, we detected the typical osteo-differentiation markers by RT-qPCR and demonstrated that RUNX2, OC, OPN and COLL1 were greatly increased in RBP4-overexpressed MC3T3-E1 cells compared to the control. Therefore, our data suggest that RBP4 plays a positive role during osteogenesis and may be favorable for bone formation. This study provides us a new opinion about the role of RBP4 in craniosynostosis and RBP4 is worth of further study about its application on bone regeneration or bone development.