The orphan GPR50 receptor interacting with TβRI induces G1/S-phase cell cycle arrest via Smad3-p27/p21 in BRL-3A cells

The liver has the powerful capacity to regenerate after injury or resection. In one of our previous studies, GPR50 was observed to be significantly upregulated at 6 h, following a partial hepatectomy (PH) in rat liver regeneration (LR) via gene expression profile. However, little research has been done on the regulation and mechanism of GPR50 in the liver. Herein, we observed that the overexpression of GPR50 inhibited the proliferation of BRL3A cells. To further explore the molecular mechanisms of GPR50 in the regulation of BRL-3A cell proliferation, interaction between GPR50 and transforming growth factor-beta I (T beta RI) and iTRAQ (TM) differential proteomic analysis were elucidated, which suggested that GPR50 may interact with T beta RI to activate the TGF-beta signaling pathway and arrest BRL-3A cell cycle G1/S transition. Subsequently, the potential mechanism underlying the role of GPR50 in hepatocyte growth was also explored through the addition of a signaling pathway inhibitor. These data suggested that interaction between the orphan GPR50 receptor and T beta RI induced the G1 forward slash S-phase cell cycle arrest of BRL-3A cells via the Smad3-p27/p21 pathway.

Automated summary

The orphan receptor GPR50 may interact with T beta RI to activate the TGF-beta signaling pathway and induce G1/S cell cycle arrest in BRL-3A cells through the Smad3-p27/p21 pathway.