Functional expression of adrenoreceptors in mesenchymal stromal cells derived from the human adipose tissue

Abstract

Cultured mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contains multipotent stem cells capable of originating a variety of mesenchymal cell lineages. Despite tremendous progress in MSC biology spurred by their therapeutic potential, current knowledge on receptor and signaling systems of MSCs is mediocre. Here we isolated MSCs from the human adipose tissue and assayed their responsivity to GPCR agonists with Ca(2+) imaging. As a whole, a MSC population exhibited functional heterogeneity. Although a variety of first messengers was capable of stimulating Ca(2+) signaling in MSCs, only a relatively small group of cells was specifically responsive to the particular GPCR agonist, including noradrenaline. RT-PCR and immunocytochemistry revealed expression of α1B-, α2A-, and β2-adrenoreceptors in MSCs. Their sensitivity to subtype-specific adrenergic agonists/antagonists and certain inhibitors of Ca(2+) signaling indicated that largely the α2A-isoform coupled to PLC endowed MSCs with sensitivity to noradrenaline. The all-or-nothing dose-dependence was characteristic of responsivity of robust adrenergic MSCs. Noradrenaline never elicited small or intermediate responses but initiated large and quite similar Ca(2+) transients at all concentrations above the threshold. The inhibitory analysis and Ca(2+) uncaging implicated Ca(2+)-induced Ca(2+) release (CICR) in shaping Ca(2+) signals elicited by noradrenaline. Evidence favored IP3 receptors as predominantly responsible for CICR. Based on the overall findings, we inferred that adrenergic transduction in MSCs includes two fundamentally different stages: noradrenaline initially triggers a local and relatively small Ca(2+) signal, which next stimulates CICR, thereby being converted into a global Ca(2+) signal.

Navigating the bone marrow niche: translational insights and cancer-driven dysfunction

“…Moreover, MSCs express α1B, α2A, and β2-adrenoceptors that make them responsive to norepinephrine and other signals that promote changes in their metabolic requirements. 48 Activation of the SNS leads to the rapid downregulation of CXCL12 expression and the export of HSCs and other types of immune cells into the circulation. β2-adrenoceptors on MSCs can mediate changes in osteoblast differentiation and, ultimately, bone remodelling.…”

“…β2-adrenoceptors on MSCs can mediate changes in osteoblast differentiation and, ultimately, bone remodelling. 48 …”

Arginine vasopressin inhibits adipogenesis in human adipose-derived stem cells

“…The V1a receptor blocker V2255 inhibited the responses to AVP in a concentration-dependent manner, which is consistent with the RTPCR data showing V1a gene expression in hASCs. Since receptors coupled to Gq proteins in hASCs activate the PLC enzyme (Kotova et al, 2014), we utilized U73122, a PLC inhibitor to test whether it mediated the effects of AVP. Indeed, pretreatment of cells with U73122 inhibited the Ca 2+ signals, but not U73343, an inactive analog.…”

“…Interestingly, nicotine stimulates AVP secretion and may in part explain why cigarette smokers gain weight after they stop smoking (Thorgeirsson et al, 2013). Although Ca 2+ signals are reported in hASCs (Kotova et al, 2014), the mechanism by which AVP increases intracellular Ca 2+ and its role on adipogenesis is unknown. In this study, we characterized the AVP receptor subtype, its signaling pathway and impact on adipocyte differentiation.…”

Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner

“…Since the α2 adrenoceptor, peripheral benzodiazepine receptor, and GABAA receptor are expressed on human MSCs [29][30][31][32], we hypothesized that the influence of the sedatives on hBM-MSCs might be associated with their receptors. In the present study, the expression of α2-adrenoceptor, benzodiazepine receptor, and GABAA receptor on hBM-MSCs was confirmed by qRT-PCR.…”