Related Experiment Video

Updated: Jun 25, 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

400

IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease

Xiaochen Wang1, Yifan Zhang1, Kun Chi1

  • 1Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, 100853, China.

Apoptosis : an International Journal on Programmed Cell Death
|May 25, 2024
PubMed

Insights

Insulin-like growth factor-binding protein 2 (IGFBP2) drives podocyte apoptosis in diabetic kidney disease (DKD). Blocking IGFBP2 or its pathway (ITGA5/FAK) protects against DKD progression and kidney damage.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Podocyte apoptosis is central to diabetic kidney disease (DKD) pathogenesis.
  • Insulin-like growth factor-binding protein 2 (IGFBP2) is implicated in inflammation and apoptosis, with elevated levels in DKD patients, but its precise role is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which IGFBP2 contributes to podocyte apoptosis in DKD.
  • To investigate IGFBP2's role in DKD progression and identify potential therapeutic targets.

Main Methods:

  • Studied IGFBP2 levels in diabetic mice and high glucose conditions.
  • Utilized STZ-induced DKD mouse models with IGFBP2 deficiency, knockdown, or deletion.
  • Investigated the role of integrin α5 (ITGA5) and focal adhesion kinase (FAK) in IGFBP2-mediated podocyte apoptosis.
  • Assessed mitochondrial injury markers like membrane potential and ROS production.

Main Results:

  • IGFBP2 levels were significantly increased in diabetic states and high glucose.
  • IGFBP2 deficiency or knockdown attenuated DKD markers (urine protein, renal injury, glomeruli hypertrophy) and podocyte apoptosis.
  • IGFBP2 induced podocyte apoptosis via ITGA5 binding, leading to FAK phosphorylation and mitochondrial dysfunction (decreased membrane potential, increased ROS).
  • ITGA5 knockdown or FAK inhibition reversed high glucose- or IGFBP2-induced podocyte apoptosis.

Conclusions:

  • IGFBP2 promotes podocyte apoptosis in DKD through the ITGA5/FAK-mediated mitochondrial injury pathway.
  • Targeting the IGFBP2-ITGA5-FAK axis offers a potential therapeutic strategy for diabetic kidney disease.
Keywords:
Diabetic kidney diseaseFAKIGFBP2Mitochondrial damageROS

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

556
Author Spotlight: Understanding Retinal Vessel Resilience and Disease Progression04:36

Author Spotlight: Understanding Retinal Vessel Resilience and Disease Progression

Published on: January 12, 2024

1.1K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.7K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
181