Pericytes secrete pro-regenerative molecules in response to platelet-derived growth factor-BB

Abstract

Brain pericytes not only maintain the anatomical, biochemical and immune blood-brain barrier, but display features of mesenchymal stem cells (MSCs) in vitro. MSCs have pro-regenerative properties attributed to their secretome. However, whether also brain pericytes possess such pro-regenerative capacities is largely unknown. Here we characterize the secretome and microvesicle (MV) release of human brain pericytes mediated by platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor beta (PDGFRβ) signalling. Upon PDGF-BB, pericytes release not only a plethora of growth factors and a panel of cytokines, but also MVs containing BDNF, FGFb, βNGF, VEGF and PLGF, a response that is specific for PDGFRβ signalling and activation of the ERK 1/2 pathway. In contrast, lipopolysaccharide (LPS), an activator of the innate immune system, stimulates the secretion of much higher amounts of mainly inflammatory cytokines and activates the NFκB pathway. Pericytes change their morphology and undergo opposite changes in surface marker expression, respectively. Our findings provide evidence that the secretome of human brain pericytes varies greatly depending on the exogenous stimulus. The differential secretory functions of pericytes may play an important role in either regulating neuroinflammation or contributing to neurorestoration and identify a possible new target cell for neuroregeneration.

Regulator of G‐protein signaling 5 regulates the shift from perivascular to parenchymal pericytes in the chronic phase after stroke

“…Another possible explanation for the reduced protein levels of PDGFR-β in WT mice could be that activation of the PDGFR-β pathway led to internalization of PDGFR-β and thereby reduction in the total PDGFR-β protein. We and others have previously shown that stimulation of PDGFR-β results in decreased surface expression and internalization, which are associated with increased phosphorylation of the receptor (30–34). The increased activation of PDGFR-β as indicated by the increased ratio of pPDGFR-β to total PDGFR-β in WT mice might facilitate pericyte detachment from the vessels and increase the density of parenchymal pericytes.…”

Pericyte-Mediated Tissue Repair through PDGFRβ Promotes Peri-Infarct Astrogliosis, Oligodendrogenesis, and Functional Recovery after Acute Ischemic Stroke

“…4). Among possible factors produced by PDGFRb -positive cells, we focused on IL6 because it can be produced from mesenchymal cells, including pericytes (Gaceb et al, 2018), and can induce the phosphorylation of STAT3 and AKT, both potent intracellular transducers of activation and survival/proliferation of astrocytes (Yamashita et al, 2005;Nakamura et al, 2012;Wanner et al, 2013;Gu et al, 2016). It is also reported that IL6 can induce poststroke angiogenesis and repair (Gertz et al, 2012).…”

Neuroinflammation, oxidative stress, and blood-brain barrier (BBB) disruption in acute Utah electrode array implants and the effect of deferoxamine as an iron chelator on acute foreign body response

“…The complete role of pericytes in the CNS is still not fully understood. Pericytes secrete several angiogenic factors and pro-regenerative molecules [214, 215] and maintain the BBB. They are extremely sensitive to inflammatory factors such as MMP9, TNF, IL1B, and IL6 [216, 217] and assist in phagocytosis, cytokine secretion, transmigration of neutrophils, and blood vessel remodeling [216, 218–220].…”