Related Experiment Video

Updated: Jan 23, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

10.3K

Small GTPase Arf6 regulates diabetes-induced cholesterol accumulation in podocytes

Jijia Hu1, Qian Yang1, Zhaowei Chen1

  • 1Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.

Journal of Cellular Physiology
|June 18, 2019
PubMed

Insights

High glucose in diabetic kidney disease (DKD) impairs podocyte cholesterol regulation by downregulating ADP-ribosylation factor 6 (Arf6), leading to cellular injury. This suggests Arf6 is crucial for maintaining podocyte health in DKD.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Metabolic Diseases

Background:

  • Podocyte injury is central to diabetic kidney disease (DKD) progression.
  • Intracellular cholesterol accumulation is linked to podocyte injury, but its cause in DKD remains unclear.
  • ADP-ribosylation factor 6 (Arf6) influences cholesterol homeostasis by regulating transporter recycling.

Purpose of the Study:

  • To investigate the role of Arf6 in modulating cholesterol metabolism within podocytes.
  • To examine the effect of Arf6 on the cholesterol transporter ABCA1 in podocytes.
  • To elucidate the mechanisms of podocyte cholesterol disorders in DKD.

Main Methods:

  • Studied Arf6's effect on ATP-binding cassette transporter 1 (ABCA1) recycling in podocytes in vivo and in vitro.
  • Utilized streptozotocin-induced diabetic rat models.
  • Assessed intracellular cholesterol levels and Arf6 expression under high-glucose conditions.

Main Results:

  • Podocytes from diabetic rats showed increased intracellular cholesterol.
  • Hyperglycemia downregulated Arf6 expression in podocytes.
  • Arf6 knockdown exacerbated cholesterol accumulation and ABCA1 recycling disorders under high-glucose conditions.

Conclusions:

  • Downregulation of Arf6 in DKD leads to ABCA1 recycling defects.
  • This recycling disorder contributes to high-glucose-induced cholesterol accumulation and podocyte injury.
  • Arf6 plays a significant role in protecting podocytes from cholesterol overload in DKD.
Keywords:
ABCA1Arf6cholesteroldiabetic kidney diseasepodocytes

More Related Videos

Guided Differentiation of Mature Kidney Podocytes from Human Induced Pluripotent Stem Cells Under Chemically Defined Conditions08:06

Guided Differentiation of Mature Kidney Podocytes from Human Induced Pluripotent Stem Cells Under Chemically Defined Conditions

Published on: July 2, 2020

5.0K
Author Spotlight: Generation of Patient-Derived Podocytes from Skin Biopsies08:52

Author Spotlight: Generation of Patient-Derived Podocytes from Skin Biopsies

Published on: May 26, 2023

3.0K

Related Concept Videos

GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.8K
GTPases and their Regulation02:14

GTPases and their Regulation

2.9K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
1.3K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.2K
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
4.3K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K