LncRNA MEG3 restrained pulmonary fibrosis induced by NiO NPs via regulating hedgehog signaling pathway‐mediated autophagy

Abstract

Long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) was downregulated in pulmonary fibrosis of rats induced by Nickel oxide nanoparticles (NiO NPs), while the downstream regulatory mechanisms of MEG3 remain unclear. This study aimed to investigate the relationship among MEG3, Hedgehog (Hh) signaling pathway and autophagy in pulmonary fibrosis caused by NiO NPs. The pulmonary fibrosis model in rats was constructed by intratracheal instillation of 0.015, 0.06, and 0.24 mg/kg NiO NPs twice a week for 9 weeks. Collagen deposition model was established by treating A549 cells with 25, 50, and 100 μg/mL NiO NPs for 24 h. Our results indicated that NiO NPs activated Hh pathway, down-regulated the expression of MEG3, and reduced autophagy activity in vivo and in vitro. Meanwhile, the autophagy process was promoted by Hh pathway inhibitor (CDG-0449), while the collagen formation in A549 cells was reduced by autophagy activator (Rapamycin). Furthermore, the overexpressed MEG3 inhibited the activation of Hh pathway, resulting in autophagy activity enhancement along with collagen formation reduction. In summary, lncRNA MEG3 can restrain pulmonary fibrosis induced by NiO NPs via regulating hedgehog signaling pathway-mediated autophagy, which may serve as a potential therapeutic strategy for pulmonary fibrosis.

Danshensu methyl ester enhances autophagy to attenuate pulmonary fibrosis by targeting lncIAPF–HuR complex

“…Regarding lncRNA-related autophagy in pulmonary fibrosis, studies have reported that lncRNAs are involved in autophagy regulation. lncRNA-MEG3 restrained pulmonary fibrosis induced by NiO NPs via regulating autophagy mediated by the Hedgehog Frontiers in Pharmacology frontiersin.org signaling pathway (Gao et al, 2022). lncIAPF promotes fibroblast-to-myofibroblast differentiation to accelerate pulmonary fibrosis through lncIAPF-mediated autophagic flux in vivo and in vitro in patients with idiopathic pulmonary fibrosis (IPF).…”

LncRNA MEG3: Potential stock for precision treatment of cardiovascular diseases

“…Downregulation of MEG3 or FOXO1 can lead to decreased autophagy of INS-1 cells induced by high glucose. 1 During pulmonary fibrosis, downregulation of MEG3 activates the Hedgehog (Hh) signaling pathway and inhibits autophagy activity of A549 cells ( Gao et al, 2022 ). Autophagy exists in tumor cells, and downregulation of MEG3 can partially inhibit autophagy in lung cancer cells and can also regulate ATG3 activity to inhibit autophagy in epithelial ovarian cancer cells.…”

Serum non‐coding RNAs for diagnosis and stage of liver fibrosis

“…Its loss of expression has been observed in different types of cancer such as liver cancer, lung cancer, gastric cancer, and so on 76–78 . Research showed MEG3 played an important role in fibrosis diseases, such as liver fibrosis, pulmonary fibrosis, renal fibrosis, and cardiac fibrosis 79–82 . MEG3 played an inhibitory role in the activation of HSC and the expression of MEG3 decreased both in vivo and in vitro during fibrosis progression 83,84 .…”

“…[76][77][78] Research showed MEG3 played an important role in fibrosis diseases, such as liver fibrosis, pulmonary fibrosis, renal fibrosis, and cardiac fibrosis. [79][80][81][82] MEG3 played an inhibitory role in the activation of HSC and the expression of MEG3 decreased both in vivo and in vitro during fibrosis progression. 83,84 These results indicated that MEG3 might be a potential marker for liver fibrosis.…”