S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype

Abstract

S100B is a biomarker of nervous system injury, but it is unknown if it is also involved in vascular injury. In the present study, we investigated S100B function in vascular remodeling following injury. Balloon injury in rat carotid artery progressively induced neointima formation while increasing S100B expression in both neointimal vascular smooth muscle (VSMC) and serum along with an induction of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA delivered by adenoviral transduction attenuated the PCNA expression and neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation and migration in vitro. Conversely, overexpression of S100B promoted VSMC proliferation and migration. Mechanistically, S100B altered VSMC phenotype by decreasing the contractile protein expression, which appeared to be mediated by NF-κB activity. S100B induced NF-κB-p65 gene transcription, protein expression and nuclear translocation. Blockade of NF-κB activity by its inhibitor reversed S100B-mediated downregulation of VSMC contractile protein and increase in VSMC proliferation and migration. It appeared that S100B regulated NF-κB expression through, at least partially, the Receptor for Advanced Glycation End products (RAGE) because RAGE inhibitor attenuated S100B-mediated NF-κB promoter activity as well as VSMC proliferation. Most importantly, S100B secreted from VSMC impaired endothelial tube formation in vitro, and knockdown of S100B promoted re-endothelialization of injury-denuded arteries in vivo. These data indicated that S100B is a novel regulator for vascular remodeling following injury and may serve as a potential biomarker for vascular damage or drug target for treating proliferative vascular diseases.

Gpr126/Adgrg6 contributes to the terminal Schwann cell response at the neuromuscular junction following peripheral nerve injury

“…These functions may relate to cytoplasmic process extension in the tSC; with decreased S100β expression, processes are unable to extend. The extracellular functions of S100β include promotion of injury‐induced vascular remodeling (Cao et al, ) and activation of the immune response. In macrophages, CD68 binds to specific S100β proteins to regulate immune functions (Okada et al, ).…”

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation

“…The samples were then detected at 450 nm by a microplate reader (Bio-Rad, Hercules, CA, USA), and analyzed using the mathematical formula [(OD value of test -OD value of blank)/ (OD value of control -OD value of blank)] to quantify the cell viability. In each group, three replicates were executed, and three or five independent experiments were implemented [25].…”

“…The cells were then cultured in serum-free medium containing different dosage of VEGF-A or VEGF-B, and then digital images of the scratch-wound area were acquired at 0, 4, 8 h after wounding following dying with Crystal Violet Staining Solution. The gap areas relative to those measured at 0 h after wounding were quantified [25].…”

“…It is known that PI3K/ Akt, p38 MAPK, ERK1/2, and eNOS signaling regulate VEGF expression in ECs, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) [24,25,28,32]. To test if any of these signaling pathways is involved in VNS-induced VEGF-A/B expression, we used pathway-specific inhibitors to block the above-mentioned signal individually and observe if Ach-induced VEGF expression can be altered.…”

The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions

“…S100β, a member of the S100 multigenic family expressing small (9 kDa and 14 kDa) Ca2+binding proteins of the EF-hand type, is primarily localised to astrocytes and glial cells under normal physiological conditions and is positively associated with age and various neurodegenerative and neuroinflammatory diseases (Donato et al, 2009). S100β promotes intimal thickening through interaction with the receptor for advanced glycation end-products (RAGE) (Cao et al, 2017) and induces migration and infiltration of inflammatory cells associated with cerebral ischemic disease and muscular dystrophy (Sagheddu et al, 2018;Zhou et al, 2018). Importantly, S100β appears to play a crucial role in maintaining an intermediate state of Sca1 + progenitor cells following injury-induced neointimal thickening through a RAGE and stromal cell-derived factor-1 α/CXCR4 signalling mechanism (Wu et al, 2019).…”