Apelin inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia

Abstract

Apelin is highly expressed in the lungs, especially in the pulmonary vasculature, but the functional role of apelin under pathological conditions is still undefined. Hypoxic pulmonary hypertension is the most common cause of acute right heart failure, which may involve the remodeling of artery and regulation of autophagy. In this study, we determined whether treatment with apelin regulated the proliferation and migration of rat pulmonary arterial smooth muscle cells (SMCs) under hypoxia, and investigated the underlying mechanism and the relationship with autophagy. Our data showed that hypoxia activated autophagy significantly at 24 hrs. The addition of exogenous apelin decreased the level of autophagy and further inhibited pulmonary arterial SMC (PASMC) proliferation via activating downstream phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/the mammalian target of Rapamycin (mTOR) signal pathways. The inhibition of the apelin receptor (APJ) system by siRNA abolished the inhibitory effect of apelin in PASMCs under hypoxia. This study provides the evidence that exogenous apelin treatment contributes to inhibit the proliferation and migration of PASMCs by regulating the level of autophagy.

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

“…It was reported that the administration of TOCP resulted in the change of autophagy-related protein expression and a significant inhibition of autophagy activity in neurons of hens, which suggested that dysfunction of autophagy-regulated machinery in neurons might be involved in the pathogenesis of OPIDN [20,21]. Recent researches illuminated that Apelin could regulate the autophagy in vivo and vitro model [30,31]. In this study, we investigated whether the autophagy was involved in the action mechanism which Apelin-13 prevented against the delayed neuropathy induced by TOCP.…”

“…The studies showed that Apelin could regulate the level of autophagy. Zhang et al [30] elucidated that exogenous Apelin treatment contributed to inhibit the proliferation and migration of pulmonary arterial smooth muscle cells by regulating the level of autophagy. Bao et al [31] found that the autophagy might be involved in the mechanism of Apelin-13 attenuating traumatic brain injury-induced damage.…”

Protective effects of luteolin-7-O-glucoside against starvation-induced injury through upregulation of autophagy in H9c2 Cells

“…Autophagy is induced by nutrient starvation through the inhibition of mTOR, resulting in translocation of the mTOR substrate complex from the cytosol to certain domains of the endoplasmic reticulum (ER) or closely attached structures (15,16). Otherwise, activation of the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway, by expressing an active form of Akt, or expressing a constitutively active form of 3-phosphoinositide-dependent protein kinase 1 (PDK1), has an inhibitory effect on autophagy (10,17). The mTOR signaling pathway is critical because of its ability to integrate the information from nutrient, metabolic and hormonal signals (10,18).…”

Apelin/APJ signaling in hypoxia-related diseases

“…In addition, apelin protects against ischemic brain injury by activating the PI3K/AKT-dependent manner. Eyries et.al [15] Casals et.al [19] Ronkainen et.al [20] Kong et.al [21] Cox et.al [22] Sheikh et.al [23] Zhang et.al [24] Glassford et.al [25] Geiger et.al [26] Kunduzova et.al [27] Sorli et.al [28 ] Heo et.al [29] Masri et.al [30] Han et.al [31] Wang et.al [32] Lu et.al [33] Andersen et.al [34] Melgar et.al [35] Kerkela et.al [36] Li et.al [37] Poirier et.al [38] Yang et.al [39] Loewen et.al [40] MEECs, Kasai et.al [41] Zhang et.al [52] Zeng et.al [59] Zhang et.al [74] Michailido u et.al [86] cardiomyocytes ROP patients…”

“…shown that exogenous apelin inhibits the autophagy and reduces the proliferation of PASMCs through the PI3K / Akt / mTOR signaling pathway [52] . However, Li F et al…”