The Role of Macula Densa Nitric Oxide Synthase 1 Beta Splice Variant in Modulating Tubuloglomerular Feedback

Liu, Ruisheng; Juncos, Luis A.; Liu, Yan; Jin, Wei; Zhang, Jie; Wang, Lei; Lai, En Yin; Carlström, Mattias; Persson, A. Erik G.

doi:10.1002/cphy.c210043

Comprehensive Physiology 2023

DOI: 10.1002/cphy.c210043

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The Role of Macula Densa Nitric Oxide Synthase 1 Beta Splice Variant in Modulating Tubuloglomerular Feedback

Ruisheng Liu

Luis A. Juncos

Yan Liu

et al.

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Cited by 2 publications

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“…8 The impaired renal autoregulation permits alterations of systemic blood pressure transmitting to the glomeruli, which elevates intraglomerular pressure and indues injury. 9 This could be one of the reasons that inconsistent observations were reported in MMP2 KO mice 10 because some mouse strains are very resistant to the development of hypertensive and diabetic kidney injury.…”

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Matrix Metalloproteinase 2 Is Crucial for Hypertension- and Hyperglycemia-Induced Kidney Injury Independent of Blood Pressure

Liu,

Staruschenko

2023

Journal of Cardiovascular Pharmacology

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I n the United States, kidney diseases are a leading cause of death. According to the Center for Disease Control and Prevention, approximately 37 million US adults are estimated to have chronic kidney disease (CKD). Diabetes and high blood pressure are the leading causes of kidney failure, accounting for 3 of 4 new cases. Primary preventions, like glycemic control, control of blood pressure, and lifestyle modifications, have shown promising benefits. However, very few drugs are available to retard CKD progression, despite extensive basic and clinical research.Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that cleave the various components of extracellular matrix. 1 Because of their wide spectrum of activities and expression sites, MMPs are now acknowledged as key players in the regulation of both cell-cell and cell-extracellular matrix interactions in tissue repair and remodeling in response to injury and the progression of diseases. 2 In this issue of the Journal, Hirata et al 3 shed new light on the potential therapeutic significance of MMP-2 in CKD. This study examined the role of MMP-2 in the development of kidney injury in salt-sensitive (SS) hypertension and type 1 diabetes using the Dahl SS rats. To examine the role of MMP-2 on kidney injury, an MMP-2-knockout (KO) rat strain was generated using Zinc-finger nucleases technology on the SS genetic background. The authors took a complex approach to determine the contribution of MMP2 knockout in the setting of both hypertension-and hyperglycemic-induced nephropathy.The SS rats developed hypertension, proteinuria, and marked renal injury in response to a high salt diet, as previously described. The renal expression and urinary excretion of MMP2 increased significantly in the SS rats. Deletion of MMP-2 from the SS rats substantially reduced kidney injury measured by proteinuria, glomerulosclerosis, fibrosis, and podocyte injury, when fed a high-salt diet, which were at similar levels to the SS rats fed a low-salt diet. Then, an streptozotocin (STZ)-induced diabetic model in the SS rats was tested.The main advantage of STZ-treated SS rats compared with other STZ-treated saltresistant rodents is that STZ-SS rats not only develop type 1 diabetes but also have profound kidney injury. 4,5 The SS rats treated with STZ developed proteinuria and renal injury along with significantly increased renal expression and urinary excretion of MMP2, similar to SS rats fed with a high-salt diet. STZ-treated MMP-2 KO rats exhibited a significant reduction in proteinuria and the excretion of nephrin and podocalyxin in comparison with STZ-treated SS rats. Deletion of MMP-2 significantly improved glomerulus permeability in STZ-treated MMP2 KO rats compared with STZ-treated SS rats. This study provided strong evidence for the pivotal role of MMP-2 in developing kidney injury in SS hypertension and diabetes. Interestingly, these beneficial effects of MMP2 are independent of blood pressure because deletion of MMP-2 had no significant effect on blood pressure in ...

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Matrix Metalloproteinase 2 Is Crucial for Hypertension- and Hyperglycemia-Induced Kidney Injury Independent of Blood Pressure

Liu,

Staruschenko

2023

Journal of Cardiovascular Pharmacology

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Oxidative stress and the role of redox signalling in chronic kidney disease

Kishi,

Nagasu,

Kidokoro

et al. 2023

Nat Rev Nephrol

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The Role of Macula Densa Nitric Oxide Synthase 1 Beta Splice Variant in Modulating Tubuloglomerular Feedback

Cited by 2 publications

References 237 publications

Matrix Metalloproteinase 2 Is Crucial for Hypertension- and Hyperglycemia-Induced Kidney Injury Independent of Blood Pressure

Matrix Metalloproteinase 2 Is Crucial for Hypertension- and Hyperglycemia-Induced Kidney Injury Independent of Blood Pressure

Oxidative stress and the role of redox signalling in chronic kidney disease

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