Related Experiment Video

Updated: Jul 17, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

468

Knockout of Matrix Metalloproteinase 2 Opposes Hypertension- and Diabetes-induced Nephropathy

Takashi Hirata1,2, Fan Fan3, Letao Fan4

  • 1Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS.

Journal of Cardiovascular Pharmacology
|August 29, 2023
PubMed

Insights

Matrix metalloproteinase-2 (MMP2) activation significantly contributes to kidney damage in hypertension and diabetes. Inhibiting MMP2 may slow the progression of chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Chronic kidney disease (CKD) progression involves extracellular matrix accumulation, leading to end-stage renal disease.
  • Broad-spectrum matrix metalloproteinase (MMP) inhibitors have shown promise in reducing renal injury in preclinical models.
  • The specific roles of MMP isoforms, particularly MMP2, in hypertensive and diabetic nephropathy remain unclear.

Purpose of the Study:

  • To investigate the role of MMP2 in the development of proteinuria and renal injury in rat models of hypertension and diabetes.
  • To compare the effects of high salt intake and streptozotocin-induced diabetes on renal injury in wild-type and MMP2 knockout rats.

Main Methods:

  • Dahl salt-sensitive (SS) rats and MMP2 knockout (KO) rats were subjected to a high-salt diet (8% NaCl) or streptozotocin treatment to induce hypertension or diabetes, respectively.
  • Evaluated parameters included mean arterial pressure, proteinuria, glomerular injury, renal fibrosis, podocyte loss, glomerulosclerosis, renal hypertrophy, and glomerular albumin permeability.
  • Renal expression of MMP2 and transforming growth factor-beta 1 (TGFβ1) was assessed.

Main Results:

  • In hypertensive rats, MMP2 KO rats exhibited reduced proteinuria, glomerular injury, renal fibrosis, and podocyte loss compared to SS rats.
  • In diabetic rats, MMP2 KO rats showed significantly less proteinuria, glomerulosclerosis, renal fibrosis, renal hypertrophy, and albuminuria despite similar increases in blood glucose and blood pressure.
  • Glomerular filtration rate decline was significantly attenuated in diabetic MMP2 KO rats compared to diabetic SS rats.

Conclusions:

  • MMP2 activation plays a critical role in the pathogenesis of both hypertensive and diabetic nephropathy.
  • Targeting MMP2 may represent a viable therapeutic strategy to slow the progression of chronic kidney disease.
  • These findings highlight MMP2 as a key mediator in kidney damage associated with metabolic and hypertensive disorders.

More Related Videos

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

610
Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

3.3K

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
463
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
679
Hypertension II: Pathophysiology01:29

Hypertension II: Pathophysiology

Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
14
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
778
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
689
Antihypertensive Drugs: Action of Diuretics01:16

Antihypertensive Drugs: Action of Diuretics

Diuretics are antihypertensive drugs used to treat hypertension resulting from sodium and water retention. Sodium, vital for fluid balance and nerve or muscle function, is regulated by the kidneys through millions of nephrons. Blood enters nephrons via afferent arterioles, which branch into capillaries called glomeruli. These filter blood plasma, allowing water and solutes, like sodium ions, to pass through capillary walls into Bowman's capsule. The filtrate then flows through various...
812