Related Experiment Video

Updated: Jan 24, 2026

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells
04:46

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells

Published on: March 7, 2025

949

The RAGE/STAT5/autophagy axis regulates senescence in mesangial cells

Mai Shi1, Shuang Yang1, Xinwang Zhu1

  • 1Department of Nephrology, The First Hospital of China Medical University, No.155 NanjingBei Rd., Heping District, Shenyang, Liaoning 110001, China.

Cellular Signalling
|June 4, 2019
PubMed

Insights

Advanced glycation end products (AGEs) accelerate kidney aging by inhibiting autophagy via the RAGE/STAT5 pathway, leading to cellular senescence. STAT5 inhibition restores autophagy and reduces senescence, offering therapeutic targets for kidney aging.

Area of Science:

  • Nephrology
  • Cellular Biology
  • Aging Research

Background:

  • Renal aging is linked to cellular senescence and accumulation of advanced glycation end products (AGEs).
  • The molecular mechanisms connecting AGEs, kidney aging, and senescence are not fully understood.
  • The role of the receptor of advanced glycation end product (RAGE) and STAT5 in this process requires further elucidation.

Purpose of the Study:

  • To investigate the role of the RAGE/STAT5 signaling pathway in AGEs-induced kidney mesangial cell senescence.
  • To explore the interplay between AGEs, RAGE, STAT5, autophagy, and cellular senescence in renal aging.
  • To identify potential therapeutic targets for mitigating kidney aging.

Main Methods:

  • Analysis of RAGE and STAT5 levels in aged human kidneys and AGEs-treated human mesangial cells.
  • Genetic and pharmacological ablation of STAT5 in mesangial cells and Sprague-Dawley (SD) rat kidneys.
  • Assessment of cellular senescence markers (p16, β-Gal) and autophagy markers (LC3, autolysosomes).
  • Inhibition of autophagy using 3-methyladenine (3-MA) to compare its effects with RAGE/STAT5 inhibition.

Main Results:

  • Elevated RAGE and STAT5 levels were observed in aged human kidneys and AGEs-treated mesangial cells.
  • STAT5 ablation significantly reduced p16 levels and senescent cell percentage, confirming its role in AGEs-induced senescence.
  • Impaired autophagy (low LC3, fewer autolysosomes) was evident in aged tissues and cells, partially restored by STAT5 inhibition.
  • RAGE/STAT5-mediated autophagy inhibition, not direct autophagy inhibition, drives mesangial aging.

Conclusions:

  • AGEs induce kidney mesangial cell senescence and autophagy inhibition through the RAGE/STAT5 pathway.
  • RAGE/STAT5 acts as a critical link between autophagy and senescence in kidney aging.
  • Targeting the RAGE/STAT5 pathway may offer a strategy to combat renal aging and associated functional decline.
Keywords:
AgingAutophagyKidneyLosartanSTAT5

More Related Videos

A Sensitive Method to Quantify Senescent Cancer Cells09:18

A Sensitive Method to Quantify Senescent Cancer Cells

Published on: August 2, 2013

21.2K
Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry14:01

Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry

Published on: September 13, 2022

5.7K

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.7K
Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
65.7K
pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.6K
Perpendicular-Axis Theorem01:16

Perpendicular-Axis Theorem

The perpendicular-axis theorem states that the moment of inertia of a planar object about an axis perpendicular to its plane is equal to the sum of the moments of inertia about two mutually perpendicular concurrent axes lying in the plane of the body.
Consider a circular disc of mass M and radius R lying along an x-y plane. The origin lies at the center of the disc, and the z-axis is perpendicular to the disc's plane. All three axes coincide at the disc's center. The moment of inertia of this...
4.5K
Parallel-axis Theorem01:06

Parallel-axis Theorem

The parallel-axis theorem provides a convenient and quick method of finding the moment of inertia of an object about an axis parallel to the axis passing through its center of mass. Consider a thin rod as an example. There is a striking similarity between the process of finding the moment of inertia of a thin rod about an axis through its middle, where the center of mass lies, and about an axis through its end using the conventional method. In the conventional method, the concept of linear mass...
8.2K