MicroRNA-141 inhibits vascular smooth muscle cell proliferation through targeting PAPP-A

Yudong Zhang1, Bainan Chen1, Liu Ming1

  • 1Department of Peripheral Vascular, Affiliated Hospital of Shandong Traditional Chinese Medicine University Jinan, China.

Insights

Oxidized low-density lipoprotein (ox-LDL) suppresses miR-141, promoting vascular smooth muscle cell (VSMC) proliferation. Restoring miR-141 or inhibiting its target PAPPA may offer therapeutic strategies for atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • RNA Biology

Background:

  • Atherosclerosis involves vascular smooth muscle cell (VSMC) proliferation, often induced by oxidized low-density lipoprotein (ox-LDL).
  • MicroRNAs (miRNAs) are regulators of cell proliferation in various conditions, but their specific role in ox-LDL-induced VSMC proliferation remains unclear.

Purpose of the Study:

  • To investigate the role and function of specific miRNAs in ox-LDL-induced VSMC proliferation.
  • To identify potential molecular targets of these miRNAs in the context of atherosclerosis.

Main Methods:

  • Quantitative real-time PCR to measure miR-141 expression.
  • Cell proliferation assays to assess VSMC growth.
  • Western blotting to detect PAPPA protein levels.
  • Luciferase reporter assays to confirm direct targeting of PAPPA by miR-141.

Main Results:

  • Ox-LDL treatment significantly suppressed miR-141 expression in VSMCs.
  • Inhibition of miR-141 led to increased VSMC proliferation.
  • PAPPA was identified as a direct target gene of miR-141.
  • Overexpression of PAPPA partially reversed the inhibitory effect of miR-141 on VSMC proliferation.

Conclusions:

  • miR-141 plays a critical role in regulating VSMC proliferation under ox-LDL stimulation.
  • The miR-141/PAPPA axis is implicated in the pathogenesis of ox-LDL-induced VSMC proliferation.
  • Targeting miR-141 or its downstream effectors may represent a novel therapeutic approach for atherosclerosis.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
8.3K