G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Abstract

G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

Single‐Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus‐Associated (HPVA) and Non‐HPVA Adenocarcinoma

“…Regarding macrophages, we discovered that the SPP1/C1QC dichotomy of macrophages was more reasonable than the classic M1/M2 classification in CC, further supporting previous studies. [ 30,41 ] In terms of DCs, we identified that CLEC9A+ DCs exerted positive antigen presentation, while LAMP3C+ DCs were related to apoptosis, which implied a mature and exhaustion‐like functional state concordant with previous researches. [ 42,43 ] Notably, we discovered CD8+ T ex cells expressing immune checkpoints, including not only PDCD1 but also TIGIT and CD96 , which have already aroused great interests as novel immune checkpoint targets.…”

Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression

“…GRK2 plays a key role in the development of many cardiovascular diseases [16]. High levels of cardiac GRK2 are associated with the induction of cardiac hypertrophy and fibrosis [20,37]. Consistently, in this study, the ISO-induced CH model showed a significant increase in GRK2 expression.…”

Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging

“…The C1QC+/SPP1+ tumor‐associated macrophage (TAM) dichotomy was first noted in colorectal cancer (CRC) by Lei Zhang et al [ 29 ] and it was confirmed by Xiong Li et al that this dichotomy could discriminate cervical cancer patients with different prognoses. [ 48 ] Thus, it was feasible to apply this ubiquitous macrophage classification in our study. C1QC+ TAMs were reported to play roles in immunosurveillance, while SPP1+ TAMs played a protumorigenic/prometastatic role in tumors.…”