G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes

Hypertension and diabetes are two common causes of chronic kidney disease. Hypertension can induce renal vascular injury, glomerular damage, podocyte loss, and tubular injury, leading to tubulointerstitial fibrosis. A number of factors influence the regulation of hypertension, among which G-protein-...

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Main Authors: Huidi Tang, Kang Li, Zhan Shi, Jichao Wu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/10/729
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author Huidi Tang
Kang Li
Zhan Shi
Jichao Wu
author_facet Huidi Tang
Kang Li
Zhan Shi
Jichao Wu
author_sort Huidi Tang
collection DOAJ
description Hypertension and diabetes are two common causes of chronic kidney disease. Hypertension can induce renal vascular injury, glomerular damage, podocyte loss, and tubular injury, leading to tubulointerstitial fibrosis. A number of factors influence the regulation of hypertension, among which G-protein-coupled receptors (GPCRs) have been studied extensively because they are desirable targets for drug development. Compared to hypertension, the regulatory effects of GPCRs on hypertensive kidney disease (HKD) are less generalized. In this review, we discussed the GPCRs involved in hypertensive kidney disease, such as angiotensin II receptors (AT1R and AT2R), Mas receptor (MasR), Mas-related G-protein-coupled receptor member D (MrgD), relaxin family receptor 1 (RXFP1), adenosine receptors (A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub>, and A<sub>3</sub>), purinergic P2Y receptors, and endothelin receptors (ET<sub>A</sub> and ET<sub>B</sub>). The progression of HKD is rarely reversed but can be retarded by ameliorating the hypertensive microenvironment in the kidneys. However, simply reducing blood pressure cannot stop the progression of HKD. Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD), which is a major cause of morbidity and mortality in diabetes. Many GPCRs are involved in DN. Here, we select some well-studied GPCRs that are directly associated with the pathogenesis of DN to illustrate their mechanisms. The main purpose of this review is to provide an overview of the GPCRs involved in the occurrence and progression of HKD and DN and their probable pathophysiological mechanisms, which we hope will help in developing new therapeutic strategies.
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spelling doaj-art-2c0c8b2c829e46778e26d6b3d3911b512025-08-20T03:14:32ZengMDPI AGCells2073-44092025-05-01141072910.3390/cells14100729G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and DiabetesHuidi Tang0Kang Li1Zhan Shi2Jichao Wu3Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, ChinaDepartment of Pharmacology, Shandong University School of Medicine, Jinan 250012, ChinaDepartment of Pharmacology, Shandong University School of Medicine, Jinan 250012, ChinaDepartment of Pharmacology, Shandong University School of Medicine, Jinan 250012, ChinaHypertension and diabetes are two common causes of chronic kidney disease. Hypertension can induce renal vascular injury, glomerular damage, podocyte loss, and tubular injury, leading to tubulointerstitial fibrosis. A number of factors influence the regulation of hypertension, among which G-protein-coupled receptors (GPCRs) have been studied extensively because they are desirable targets for drug development. Compared to hypertension, the regulatory effects of GPCRs on hypertensive kidney disease (HKD) are less generalized. In this review, we discussed the GPCRs involved in hypertensive kidney disease, such as angiotensin II receptors (AT1R and AT2R), Mas receptor (MasR), Mas-related G-protein-coupled receptor member D (MrgD), relaxin family receptor 1 (RXFP1), adenosine receptors (A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub>, and A<sub>3</sub>), purinergic P2Y receptors, and endothelin receptors (ET<sub>A</sub> and ET<sub>B</sub>). The progression of HKD is rarely reversed but can be retarded by ameliorating the hypertensive microenvironment in the kidneys. However, simply reducing blood pressure cannot stop the progression of HKD. Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD), which is a major cause of morbidity and mortality in diabetes. Many GPCRs are involved in DN. Here, we select some well-studied GPCRs that are directly associated with the pathogenesis of DN to illustrate their mechanisms. The main purpose of this review is to provide an overview of the GPCRs involved in the occurrence and progression of HKD and DN and their probable pathophysiological mechanisms, which we hope will help in developing new therapeutic strategies.https://www.mdpi.com/2073-4409/14/10/729hypertensionhypertensive kidney diseaseGPCRdiabetic nephropathy
spellingShingle Huidi Tang
Kang Li
Zhan Shi
Jichao Wu
G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
Cells
hypertension
hypertensive kidney disease
GPCR
diabetic nephropathy
title G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
title_full G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
title_fullStr G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
title_full_unstemmed G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
title_short G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes
title_sort g protein coupled receptors in chronic kidney disease induced by hypertension and diabetes
topic hypertension
hypertensive kidney disease
GPCR
diabetic nephropathy
url https://www.mdpi.com/2073-4409/14/10/729
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AT jichaowu gproteincoupledreceptorsinchronickidneydiseaseinducedbyhypertensionanddiabetes