miR-21 Exerts Anti-proliferative and Pro-apoptotic Effects in LPS-induced WI-38 Cells via Directly Targeting TIMP3.
Cell Biochem Biophys
; 79(4): 781-790, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-33942238
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which was caused by a complex interplay of inflammatory responses and chronic damage. miR-21 is increased in patients with IPF, but its function in the embryonic lung-derived diploid fibroblasts cells subjected to LPS is elusive. miRNA expression profile was obtained from GEO database and target genes of miRNAs were forecasted by TargetScan. To mimic the LPS-induced injury, different concentrations of LPS were applied to treat WI-38 cells. Functional in vitro experiments were conducted to examine the role of miR-21 and TIMP3. Luciferase report assay was performed to verify the relationship between miR-21 and TIMP3. qRT-PCR, western blotting, and ELISA were conducted to detect the levels of the related miRNAs, proteins, and inflammatory factors. miR-21 presented higher levels in interstitial pneumonia patients and LPS-induced WI-38 cells. Overexpression of miR-21 was negatively correlated with the proliferative capability of LPS-treated WI-38 cells. miR-21 directly targets TIMP3. TIMP3 restored the suppressive impact of miR-21 mimic on the proliferation, while TIMP3 alleviated the promoting impact of miR-21 mimic on the apoptosis of WI-38 cells treated by LPS. miR-21 inhibited Bcl-2 but increased Bax, cleaved caspase-3, and cleaved caspase-9. Besides, miR-21 elevated the levels of IL-6 and IL-ß but reduced the IL-10, which were weakened by TIMP3. Totally, miR-21 aggravated the LPS-induced lung injury and modulated inflammatory responses by targeting TIMP3.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
Idioma:
En
Revista:
Cell Biochem Biophys
Assunto da revista:
BIOFISICA
/
BIOQUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China