Figure 4.

Tepro inhibition of M22 stimulation of hyaluronan production is dependent on TSHR/IGF1R crosstalk in TEDOFs. TEDOFs transfected with nontargeting (NT) or β-arrestin 1 (ARRB1) siRNA were stimulated with 1 nM M22 with or without 1 µg/mL Tepro. Cells treated with ARRB1 siRNA exhibited at least a 70% decrease in ARRB1 mRNA. Secreted hyaluronan (HA) was measured in the conditioned media as described in the Materials and Methods. Data were normalized to percent maximum of M22 in cells exposed to NT siRNA, and data points depict mean ± SEM computed from the averages of triplicate measurements in 3 different TEDOF strains. Under control conditions (black bars), basal HA secretion was 9% of M22 alone, P < 0.0001. Partial inhibition by Tepro lowered HA secretion to 60%, P < 0.0001. Following ARRB1 knockdown (gray bars), HA secretion was 85% for both M22 alone and M22 + Tepro.