Related Experiment Video

Updated: Sep 21, 2025

Isolation of Murine Coronary Vascular Smooth Muscle Cells
08:24

Isolation of Murine Coronary Vascular Smooth Muscle Cells

Published on: May 30, 2016

14.3K

DR1 Activation Inhibits the Proliferation of Vascular Smooth Muscle Cells through Increasing Endogenous H2S in

Yuxin Xi1, Xin Wen1, Yuanzhou Zhang2

  • 11Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang, China.

Aging and Disease
|June 3, 2022
PubMed

Insights

Diabetic microangiopathy involves smooth muscle cell proliferation. Activating dopamine D1 receptors (DR1) boosts hydrogen sulfide (H2S) production, inhibiting this proliferation by targeting key growth factor pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Diabetology

Background:

  • Diabetic microangiopathy is linked to vascular smooth muscle cell (VSMC) proliferation and reduced endogenous hydrogen sulfide (H2S).
  • H2S is known to inhibit VSMC proliferation, but its role in diabetic complications requires further elucidation.
  • Decreased H2S and its key enzyme, cystathionine gamma-lyase (CSE), are observed in diabetic conditions, alongside altered proliferation markers.

Purpose of the Study:

  • To investigate the role of dopamine D1-like receptors (DR1) in regulating H2S production and VSMC proliferation in diabetes.
  • To explore the molecular mechanisms by which DR1 activation impacts VSMC growth and related signaling pathways.
  • To determine if DR1 agonists can mitigate diabetes-induced VSMC abnormalities.

Main Methods:

  • Assessed endogenous H2S levels and CSE expression in arterial SMCs from diabetic mice.
  • Examined the expression of proliferation markers (PCNA, Cyclin D1, p21) in diabetic and treated mice.
  • Utilized cell experiments to investigate the effects of DR1 agonist SKF38393 and H2S donor NaHS on VSMC proliferation and signaling pathways.
  • Measured intracellular calcium ([Ca2+]i) and calmodulin (CaM) activation.
  • Analyzed the modulation of growth factor signaling pathways, including IGF-1/IGF-1R, HB-EGF/EGFR, and downstream effectors (PI3K/Akt, JAK2/STAT3, ERK1/2).

Main Results:

  • Diabetic mice exhibited decreased H2S and CSE expression, with increased PCNA and Cyclin D1, and decreased p21.
  • Administration of DR1 agonist SKF38393 and H2S donor NaHS reversed these changes, increasing CSE and normalizing proliferation markers.
  • SKF38393 increased intracellular calcium and activated CaM, thereby enhancing the CSE/H2S pathway.
  • Both SKF38393 and NaHS inhibited the IGF-1/IGF-1R and HB-EGF/EGFR signaling pathways and their downstream effectors.
  • These interventions effectively inhibited high glucose-induced VSMC proliferation.

Conclusions:

  • DR1 activation up-regulates the CSE/H2S system via Ca2+-CaM signaling.
  • This mechanism inhibits key growth factor pathways (IGF-1/IGF-1R, HB-EGF/EGFR) and their downstream signaling cascades.
  • DR1 activation represents a potential therapeutic strategy to inhibit VSMC proliferation and treat diabetic microangiopathy.
Keywords:
Dopamine 1-like receptorsH2Sdiabetesvascular smooth muscle cells

More Related Videos

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

3.9K
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function06:14

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Published on: June 11, 2017

8.5K

Related Concept Videos

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...
2.7K
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
663
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...
958
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
807
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...
271