The roles of G protein-coupled receptor kinase 2 in renal diseases.

Autor: Du J; Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China., Wu X; Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.; Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China., Ni L; Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Oct; Vol. 28 (20), pp. e70154.
DOI: 10.1111/jcmm.70154
Abstrakt: G protein-coupled receptor (GPCR) kinase 2 (GRK2) is an integrative node in many signalling network cascades. An emerging study indicates that GRK2 can interact with GPCRs and non-GPCR substrates in both kinase-dependent and -independent modes. Alterations in the functional levels of GRK2 have been found in a variety of renal diseases, such as hypertension-related kidney injury, sepsis-associated acute kidney injury (S-AKI), cardiorenal syndrome (CRS), acute kidney injury (AKI), age-related kidney injury or hyperglycemia-related kidney injury. Abnormal GRK2 expression contribute to the development of renal diseases, making them promising molecular targets for treating renal diseases. Blocking the prostaglandin E 2 (PGE 2 )-EP1-Gaq-Ca 2+ signal pathway in glomerular mesangial cells (GMCs) by internalizing prostaglandin E 2 receptor 1 (EP1) with GRK2 may be a potential treatment for diabetic nephropathy (DN). In addition, GRK2 inhibition may have therapeutic effects in a variety of renal diseases, such as SLE-related kidney injury, DN, age-related kidney injury, hypertension-related kidney injury, and CRS. However, there is still a long way to go for the large-scale application of GRK2 inhibition in the field of renal diseases. In this review, we discuss recent updates in understanding the role of GRK2 in kidney dysfunction. Furthermore, we explore the potential of GRK2 as a possible therapeutic target for renal pathologies. We believe it will shed light on the future development of small-molecule inhibitors of GRK, as well as the clinical applications in renal diseases.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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