β2 microglobulin promotes pericyte proliferation through toll-like receptor 4

Yoshino Yonezu1, Akiko Uyeda2, Hidemi Misawa3

  • 1Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, 105-8512, Japan.

PubMed

Insights

Beta-2 microglobulin (B2M) promotes mouse brain pericyte proliferation and extension in vitro. This effect is mediated through Toll-like receptor 4 (TLR4) signaling, impacting cell growth and gene expression.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Pericytes are crucial for vascular integrity and central nervous system homeostasis.
  • Beta-2 microglobulin (B2M) is linked to inflammation in aging and injury.
  • Understanding B2M's role in brain pericytes is vital for neuroinflammation research.

Purpose of the Study:

  • To investigate the effects of B2M on mouse brain pericytes.
  • To elucidate the molecular mechanisms underlying B2M's impact on pericytes.

Main Methods:

  • In vitro culture of mouse brain pericytes.
  • Treatment with B2M.
  • Assessment of proliferation using Bromodeoxyuridine (BrdU) and Ki67 staining.
  • Morphological analysis.
  • RNA sequencing (RNA-seq) for transcriptomic profiling.
  • Involvement of Toll-like receptor 4 (TLR4) was investigated.

Main Results:

  • B2M treatment increased pericyte proliferation (BrdU and Ki67 incorporation).
  • B2M induced morphological changes, promoting pericyte extension.
  • RNA-seq revealed differential gene expression related to cell proliferation.
  • TLR4 signaling was identified as a key mediator of B2M's effects on pericytes.

Conclusions:

  • B2M directly influences mouse brain pericytes.
  • B2M promotes pericyte proliferation and extension via TLR4 signaling.
  • These findings highlight B2M as a potential regulator of pericyte function in the CNS.

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...
3.3K
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...
10.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
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...
3.4K