Related Experiment Video

Updated: Mar 5, 2026

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

20.2K

Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9,

Wen-Dong Li1, Neng-Ping Li1, Dan-Dan Song1

  • 1Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

International Journal of Molecular Medicine
|March 25, 2017
PubMed

Insights

Metformin significantly inhibits endothelial progenitor cell (EPC) migration by reducing matrix metalloproteinase-2 (MMP-2) and MMP-9. This effect is mediated through the AMPK/mTOR/autophagy pathway, highlighting a novel mechanism for metformin

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Pharmacology

Background:

  • Endothelial progenitor cells (EPCs) are crucial for vascular repair.
  • EPC migration is essential for angiogenesis and neovascularization.
  • Metformin's effects on EPC function require further elucidation.

Purpose of the Study:

  • To investigate the impact of metformin on EPC migration.
  • To explore the underlying molecular mechanisms, including matrix metalloproteinase (MMP) expression and the AMPK/mTOR/autophagy pathway.

Main Methods:

  • EPCs were treated with metformin.
  • Cell migration was assessed using wound healing and Matrigel invasion assays.
  • MMP-2 and MMP-9 expression and activity were analyzed by RT-PCR, Western blot, and zymography.
  • The AMPK/mTOR/autophagy pathway was evaluated.

Main Results:

  • Metformin treatment significantly downregulated MMP-2 and MMP-9 expression and activity.
  • Metformin decreased EPC migration.
  • Increased phosphorylated AMPK (p-AMPK) and LC3II, with decreased phosphorylated mTOR (p-mTOR) and p62, were observed.
  • An AMPK inhibitor reversed metformin's effects.

Conclusions:

  • Metformin inhibits EPC migration by downregulating MMP-2 and MMP-9.
  • The AMPK/mTOR/autophagy pathway plays a critical role in mediating metformin's effects on EPCs.
  • These findings provide insights into the cardiovascular protective mechanisms of metformin.

More Related Videos

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition09:05

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition

Published on: August 20, 2016

8.4K
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

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

1.0K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
755
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...
814
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
3.6K