Table 1.
Role of GRK2 in the development of multiple fibrotic diseases.
| Type of fibrosis | Model | Relevant functional effects | Related mechanisms | References |
|---|---|---|---|---|
| Cardiac fibrosis | Isoproterenol-infused SHR | Cardiac hypertrophy; collagen I expression |
GRK2-ADRB1 | (86) |
| Myocardial infarction mice | Collagen expression; cardiac dysfunction; heart failure | GRK2-βAR | (87) | |
| HFD mice | Cardiac myofibroblast; collagen deposition | GRK2-PKA-CREB; GRK2-AMPK | (48) | |
| Myocardial infarction model by thoracotomy, CF treated with PHPS1 | Collagen I; collagen III deposition | GRK2-ERK1/2 -Smad2/3 |
(65) | |
| Neonatal rat CF treated with AVP | α-SMA; MMP2; MMP9; proliferation of CF | AVP-V1AR-GRK2 -β-arrestin-ERK1/2 |
(66) | |
| AVP-induced neonatal rat CF | Cardiac inflammation; fibroblast proliferation; cardiac remodeling | AVP-GRK2-NF-κB -IL-6 |
(80) | |
| Renal fibrosis | shGRK2 mice | ROS; ECM; inhibition of matrix degradation | GRK2-RAS-AT1R | (88) |
| HFD+STZ mice; GMCs induced by PGE2 | ECM deposition; GMCs proliferation | GRK2-β-arrestin2 -EP1 |
(89) | |
| Chronic heart failure | Inflammation; ECM | GPCRs-Gβγ-GRK2 | (90) | |
| Liver fibrosis | Human patient tissue specimens | Recruitment of neutrophils in the liver | IL-33-ST2-GRK2 -CXCR2 |
(91) |
| Cirrhotic rats induced by CCl4 | The contractility of vascular smooth muscle | GRK2-β-arrestin2 -ROCK |
(92) | |
| Porcine serum induced fibrotic rats | HSCs activation | Decreased expression of GRK2 | (93) | |
| CCl4 or thioacetamide injected mice | HSCs activation; collagen deposition | GRK2-A2AR-MMPs | (94–96) | |
| Pulmonary fibrosis | Bleomycin-induced pulmonary fibrotic mice | Recruitment of neutrophils; α-SMA; collagen-1; inflammation | GRK2-CXCR2-MIP2-IL-1β | (97) |
SHR means the spontaneously hypertensive rats; PHPS1 used to specifically inhibit SHP-2; shGRK2 mice are the GRK2 hemizygous mice.
ADRB1, adrenergic receptor beta 1; HFD, high-fat diet; CREB, cAMP-response element binding protein; AVP, arginine vasopressin; CF, cardiac fibroblast; AMPK, AMP-activated protein kinase; MMP2, matrix metallopeptidase 2; RAS, renin-angiotensin system; STZ, streptozocin; GMCs, glomerular mesangial cells; HSCs, hepatic stellate cells; ROCK, Rho-kinase inhibitors; α-SMA, alpha-smooth muscle actin; ST2, serum stimulation-2.