Related Experiment Video

Updated: Jul 5, 2026

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

SIRT6 Attenuates Angiotensin II-Induced Podocyte Cholesterol Accumulation and Injury via Negative Modulation of

Yingjie Yang1, Jingjing Ma1, Danqi Chang1

  • 1Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China.

Kidney & Blood Pressure Research
|July 3, 2026
PubMed
Abstract

Insights

Sirtuin 6 (SIRT6) protects kidney podocytes from injury by suppressing cholesterol synthesis. This finding reveals SIRT6 as a potential therapeutic target for chronic kidney disease (CKD) caused by Angiotensin II.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Angiotensin II (Ang II) contributes to chronic kidney disease (CKD) via podocyte injury, but mechanisms remain unclear.
  • Previous studies linked Ang II to reduced cholesterol efflux via Sirtuin 6 (SIRT6), causing podocyte injury.
  • The role of SIRT6 in podocyte cholesterol synthesis was previously undetermined.

Purpose of the Study:

  • To investigate the role of SIRT6 in regulating sterol regulatory element-binding protein 2 (SREBP2), a key cholesterol synthesis molecule.
  • To assess the impact of SIRT6 on cholesterol content and apoptosis in podocytes.
  • To elucidate the mechanism by which SIRT6 influences podocyte injury.

Main Methods:

  • Constructed an Ang II-infused rat model for studying kidney disease.
  • Quantified cholesterol levels and analyzed SIRT6 and SREBP2 expression using western blot and immunofluorescence.
  • Assessed podocyte apoptosis via flow cytometry and utilized SIRT6 expression plasmids to investigate its deacetylase activity's role.

Main Results:

  • Ang II increased glomerular lipid/cholesterol, decreased SIRT6, and activated SREBP2 in rats.
  • SIRT6 activation in podocytes counteracted SREBP2, reducing cholesterol accumulation and apoptosis.
  • SIRT6's suppression of SREBP2 and subsequent protective effects were dependent on its histone deacetylase activity.

Conclusions:

  • SIRT6 protects podocytes against Angiotensin II-induced injury by inhibiting cholesterol synthesis via SREBP2.
  • SIRT6 acts as a crucial regulator against Renin-Angiotensin System (RAS) activation in podocytes.
  • SIRT6 represents a novel therapeutic target for managing cholesterol-related podocyte injury in CKD.
Keywords:
Angiotensin IIApoptosisCholesterol accumulationPodocyteSIRT6SREBP2

Related Concept Videos

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,...
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...
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...
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...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...