PXD078791-1

PXD078791 is an original dataset announced via ProteomeXchange.

Title	High glucose-induced mitochondrial fission promotes Müller cell activation via suppression of the Hippo pathway
Description	Diabetic retinopathy (DR) is the leading cause of blindness in diabetic patients, in which high glucose (HG)-induced Müller cell activation constitutes a central pathological event. This study aimed to untangle the critical role and mechanism of mitochondrial fission in this process. We found that under HG conditions, the level of p-Drp1 was significantly elevated (P<0.05), driving excessive mitochondrial fission. Functional experiments confirmed that artificially enhancing mitochondrial fission directly inhibited the Hippo signaling pathway (levels of core proteins p-MST1/2, p-LATS1, and p-YAP decreased, P<0.05, and YAP translocated to the nucleus), thereby activating Müller cells (expression of marker proteins GS and Kir4.1 decreased, while expression of GFAP, AQP4, and inflammatory mediators IL-1β, IL-6, VEGF increased, P<0.05). Key rescue experiments demonstrated that Drp1 silencing (reduced p-Drp1 level, P<0.05) reversed the aforementioned activation; however, co-administration of the Hippo pathway inhibitor XMU-MP-1 re-induced cell activation, proving that the Hippo pathway is a necessary downstream mediator of mitochondrial fission. In a diabetic rat model, elevated p-Drp1, Hippo pathway inhibition, and cell activation were similarly observed; the mitochondrial fission inhibitor Mdivi-1 alleviated this pathological process, whereas XMU-MP-1 counteracted its protective effects. This study systematically elucidates, from ex vivo to in vivo, the causal regulatory axis of "HG- mitochondrial fission- Hippo pathway inhibition—Müller cell activation," providing experimental evidence and a potential target for developing DR-targeted therapeutic strategies centered on intervening in mitochondrial dynamics.
HostingRepository	iProX
AnnounceDate	2026-05-23
AnnouncementXML	Submission_2026-05-25_01:16:48.890.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bo Li
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	methionine oxidation with neutral loss of 64 Da
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-25 01:16:29	ID requested
⏵ 1	2026-05-25 01:16:49	announced

Dataset with its publication pending

submitter keyword: Müller Cells, High-Glucose, Proteomic Analysis

Hui Peng
contact affiliation	First Affiliated Hospital of Chongqing Medical University
contact email	pengh9@sina.com
lab head
Bo Li
contact affiliation	First Affiliated Hospital of Chongqing Medical University
contact email	382151973@qq.com
dataset submitter

iProX dataset URI