High density lipoprotein promoting proliferation and migration of type II alveolar epithelial cells during inflammation state

Abstract

BackgroundTo investigate the effect and mechanism of high density lipoprotein (HDL) on type II alveolar epithelial cells during inflammation state.MethodsThe original generation of type II alveolar epithelial cells were separated in rats and treated with PBS/LPS/HDL/HDL + LPS. To observe the proliferation and migration of type II alveolar epithelial cells with bromodeoxyuridine(BrdU) assay, transwell assay and wound healing experiments. In addition, western blot detected the expression of TP-binding cassette transporter A1 (ABCA1), cystic fibrosis transmembrane conductance regulator (CFTR) and the phosphorylation of AKT/extracellular signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK). Enzyme-linked immunosorbent assay (ELISA) tested the secretion of tumor necrosis factor a(TNF-a)/interleukin 1a(IL-1a)/IL-6.ResultsHDL promoted the proliferation (↑17%, p < 0.001 HDL+ LPS vs. LPS) and migration (wounding healing: ↑93%, p < 0.001 HDL+ LPS vs. LPS; transwell migration: ↑154%, p < 0.001 HDL+ LPS vs. LPS) of type II alveolar epithelial cells. Furthermore, HDL increased the phosphorylation of MAPK, but not AKT/ERK. And HDL decreased the secretion of TNF-a (↓46%, p < 0.01 HDL+ LPS vs. LPS) and IL-1a (↓45%, p < 0.001 HDL+ LPS vs. LPS), but not IL-6. In addition, HDL up-regulated the expression of ABCAI (↑99%, p < 0.001 HDL vs. CON) and down-regulated the expression of CFTR (↓25%, p < 0.05 HDL vs. CON) in type II alveolar epithelial cells.ConclusionsHDL increases the phosphorylation of MAPK, which promotes the proliferation and migration of type II alveolar epithelial cells. And it decreased the secretion of TNF-a/IL-1a and the expression of CFTR. All these suggest that HDL plays an important role in anti-inflammatory effect in inflammation state of lung.

Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel

“…At S0 and S1, the pathways related to the initial steps of wound healing, including coagulation, such as fibrin clot formation [49][50][51][52] and platelet degranulation plugs [53]; pro-inflammatory responses including complement cascade and syndecan interactions [54,55]; release of growth factors, including insulin-like growth factor [56][57][58]; and essential steps in the healing process, such as non-integrin membrane-extracellular matrix (ECM) interactions [59][60][61], were less active in patients with severe PS than in patients with mild/moderate PS. In addition, pathways involved in the protective tissue repair processes, including high-density lipoprotein assembly [62][63][64] and retinoid metabolism [65] pathways, were also downregulated in patients with severe PS. These data suggest lower wound healing activity in patients with severe PS than in patients with mild/moderate PS, in this active phase of PCM.…”

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

“…The concentration of HDL required to increase wound healing in vivo [12] was substantively higher than those used here: 800 µg protein mL −1 of HDL in 20% pluronic F-127 gel, every 2 days for 10 days, increased wound healing in apoE −/− mice by nearly 50%, compared with the pluronic gel control. Yu et al (2017) also utilised high levels of HDL (100 mg mL −1 apoA-I concentration) to achieve increases in proliferation and migration of type II alveolar epithelial cells [23], but Zhang et al (2010) employed equivalent concentrations to those used here to stimulate proliferation of endothelial progenitor cells and promote wound healing [13], via a pathway which involved activation of phosphoinositide -3-kinase (PI3K), protein kinase B (PKB; Akt1) and cyclin D.…”

“…Apolipoprotein (apo) A-I, the major protein component of HDL, and apoA-I mimetics can also promote arterial healing by reducing oxidative stress [20], and protect against impaired re-endothelialisation due to dysfunctional HDL [21], although it cannot entirely replicate the effect of HDL [22]. HDL also stimulates the proliferation and migration of type II alveolar epithelial cells during inflammation [23], and topical administration of synthetic HDL nanoparticles improves corneal re-epithelialisation in diabetic mice following wounding, and in corneas subjected to alkali-burn induced inflammation [24]; these particles also delivered microRNA (miRNA; miR) sequences to epithelial and stromal cells in an intact ocular surface [24].…”

Extracellular Lipids in the Lung and Their Role in Pulmonary Fibrosis

“…In both studies, blockade of the TGF-β signaling abolishes the activation properties of these derivatives. In alveolar epithelial cells, the addition of HDL enhances proliferation and migration properties with the activation of AKT and ERK signaling pathways [ 120 ]. It should be noted that HDL is a well-known system for the transport of cholesterol from the peripheral tissues back to the liver.…”