Regulator of G protein signaling 2 (RGS2) is a key member of the RGS family and plays a critical role in regulating G protein-coupled receptor (GPCR) signaling pathways. RGS2 accelerates the GTPase activity of Gα subunits, especially Gαq and Gαi, thereby terminating GPCR-mediated signals and fine-tuning cellular responses. The gene is involved in a variety of physiological processes, including cardiovascular regulation, immune responses, and neural signaling. Dysregulation of RGS2 has been associated with hypertension, anxiety disorders, and cancer, highlighting its therapeutic potential. The compact structure and strong selectivity of RGS2 make it an ideal target for studying GPCR dynamics and developing targeted interventions.
Human RGS2-mCherry adenoviral particles are an advanced recombinant tool designed for efficient gene delivery and visualization in mammalian cells. These particles combine the human RGS2 gene with the bright fluorescent tag mCherry, allowing real-time tracking of RGS2 expression and localization. The adenoviral vector ensures stable transduction in a variety of cell types, including primary cells and difficult-to-transfect cells, while the mCherry fusion tag allows live cell imaging and quantitative analysis without affecting RGS2 function. This system is ideal for studying the role of RGS2 in GPCR signaling, protein interactions, and their downstream effects in disease models.
Pirfenidone has recently been approved for the treatment of idiopathic pulmonary fibrosis. However, the therapeutic dose of pirfenidone is very high, resulting in side effects that limit its dose and therapeutic efficacy. Understanding the molecular mechanism of action of pirfenidone may improve its safety and efficacy. Here, researchers identified Regulator of G-protein Signaling 2 (RGS2) as an early gene induced by pirfenidone. Treatment with pirfenidone significantly increased RGS2 mRNA and protein expression in a human fetal lung fibroblast cell line and in primary lung fibroblasts isolated from patients with or without idiopathic pulmonary fibrosis. Pirfenidone treatment or direct overexpression of recombinant RGS2 in human lung fibroblasts inhibited the profibrotic effects of thrombin, whereas the absence of RGS2 exacerbated bleomycin-induced lung fibrosis and mortality in mice. Pirfenidone treatment attenuated bleomycin-induced lung fibrosis in wild-type mice but not in RGS2 knockout mice. Thus, endogenous RGS2 has an anti-fibrotic function. Upregulated RGS2 contributes significantly to the antifibrotic effect of pirfenidone.
The serine protease thrombin activates the Gq-coupled protease-activated receptor 1 (PAR1), promoting fibroblast proliferation and differentiation to a myofibroblast phenotype, leading to the development of pulmonary fibrosis. Previous studies have shown that thrombin-stimulated proliferation is dependent on PAR1-mediated increases in [Ca2+]i in multiple cell types. Because RGS2 can act as a selective modulator of Gq-mediated signaling, the researchers investigated the effect of RGS2 expression on thrombin-induced increases in [Ca2+]i in HFL1 cells. RGS2 protein was increased by about 6-fold in HFL1 cells with adenovirus-expressing RGS2 and mCherry reporter in comparison to control cells with the mCherry-expressing adenovirus alone (Figure 1a). Thrombin induced a dose-dependent increase in [Ca2+]i in control HFL1 cells expressing mCherry alone (Figure 1b). Compared with these control cells, overexpression of RGS2 significantly attenuated the thrombin (1 U/ml)-induced increase in [Ca2+]i in HFL1 cells from 3.75 ± 0.07 to 2.31 ± 0.05 (Figure 1c).
Figure 1. Increase of RGS2 attenuates thrombin-induced increase of [Ca2+]i in HFL1 cells. (Xie Y, et al., 2016)
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