LncRNA H19 initiates microglial pyroptosis and neuronal death in retinal ischemia/reperfusion injury.


Journal

Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445

Informations de publication

Date de publication:
01 2020
Historique:
received: 26 11 2018
accepted: 02 05 2019
revised: 22 04 2019
pubmed: 28 5 2019
medline: 7 4 2021
entrez: 26 5 2019
Statut: ppublish

Résumé

Ischemia-reperfusion (I/R) is a common pathology when the blood supply to an organ was disrupted and then restored. During the reperfusion process, inflammation and tissue injury were triggered, which were mediated by immunocytes and cytokines. However, the mechanisms initiating I/R-induced inflammation and driving immunocytes activation remained largely unknown. In this study, we identified long non-coding RNA (lncRNA)-H19 as the key onset of I/R-induced inflammation. We found that I/R increased lncRNA-H19 expression to significantly promote NLRP3/6 inflammasome imbalance and resulted in microglial pyroptosis, cytokines overproduction, and neuronal death. These damages were effectively inhibited by lncRNA-H19 knockout. Specifically, lncRNA-H19 functioned via sponging miR-21 to facilitate PDCD4 expression and formed a competing endogenous RNA network (ceRNET) in ischemic cascade. LncRNA H19/miR-21/PDCD4 ceRNET can directly regulate I/R-induced sterile inflammation and neuronal lesion in vivo. We thus propose that lncRNA-H19 is a previously unknown danger signals in the molecular and immunological pathways of I/R injury, and pharmacological approaches to inhibit H19 seem likely to become treatment modalities for patients in the near future based on these mechanistic findings.

Identifiants

pubmed: 31127201
doi: 10.1038/s41418-019-0351-4
pii: 10.1038/s41418-019-0351-4
pmc: PMC7206022
doi:

Substances chimiques

Apoptosis Regulatory Proteins 0
H19 long non-coding RNA 0
Inflammasomes 0
MIRN21 microRNA, mouse 0
MicroRNAs 0
RNA, Long Noncoding 0
Caspases EC 3.4.22.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

176-191

Commentaires et corrections

Type : ErratumIn

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Auteurs

Peixing Wan (P)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann arbor, MI, 48109, USA.

Wenru Su (W)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China. suwr3@mail.sysu.edu.cn.

Yingying Zhang (Y)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Zhidong Li (Z)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Caibin Deng (C)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Jinmiao Li (J)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Nan Jiang (N)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Siyu Huang (S)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Erping Long (E)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Yehong Zhuo (Y)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China. zhuoyh@mail.sysu.edu.cn.

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