Evidence map›Paper›PMID 41781544›Full record

ArticleCellular and molecular life sciences : CMLS2026

SDF2L1 modulates oxLDL-induced endoplasmic reticulum stress, protein aggregation, and O-mannosylation in myocardial infarction and lung cancer.

Huaping Tian, Tujing Zhao, Xiaoyi Huang, Hongjing Li, Lin Ye, Zheng Li, Runze Li, Ruilin Liao, Haojue Xu, Liang Zou and 2 more

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In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Huaping TianSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Tujing ZhaoSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Xiaoyi HuangSchool of Nursing, Chongqing Medical University, Chongqing, China.
Hongjing LiSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Lin YeSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Zheng LiSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Runze LiSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Ruilin LiaoSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Haojue XuDepartment of Ophthalmology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Liang ZouSchool of Food and Biological Engineering, Chengdu University, Chengdu, Sichuan, China.
Yi ShiSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Lulin HuangSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. huangluling@yeah.net.ORCID http://orcid.org/0000-0002-1204-5957

Funding

National Natural Science Foundation of China 82271105National Natural Science Foundation of China 82571240
6 · The paper itself

Abstract

backgroundOxidized low-density lipoprotein (oxLDL), formed by LDL oxidative modification, drives pathogenesis in cardiovascular diseases and cancers through ER stress, inflammation, and protein aggregation. Stromal-derived factor 2-like 1 (SDF2L1), an ER-resident chaperone, may modulate these processes, but its role in oxLDL-related pathologies remains unclear. MATERIALS AND

methodsWe analyzed spatial transcriptomic datasets from human myocardial infarction (MI) and lung cancer tissues. In vitro, we generated stable SDF2L1 knockdown (KD) or overexpression (OE) models in EA.hy926 endothelial and A549 lung epithelial cells, treated with oxLDL (10 μg/mL, 48 h). In vivo, we created global Sdf2l1 knockout (Sdf2l1−/−) mice via CRISPR-Cas9 and administered oxLDL (1.4 mg/kg i.v., 7 days). Assessments included Western blotting for ER stress markers, qPCR for inflammatory genes, PROTEOSTAT assays for protein aggregates, ELISA for O-mannosyltransferase levels, and LC–MS/MS glycoproteomics for O-mannosylation profiles.

resultsSpatial transcriptomics revealed elevated SDF2L1 in MI ischemic zones and lung cancer tissues, correlating with ATF6 (ER stress) and OLR1 (oxLDL receptor). In cells, both SDF2L1 KD and OE paradoxically exacerbated oxLDL-induced ER stress (elevated p-PERK, p-IRE1α, spliced XBP1, cleaved ATF6), inflammation (NF-κB, IL-6, NLRP3 upregulation), and protein aggregation. Sdf2l1−/− mice showed heightened oxLDL-induced ER stress, inflammatory cytokines (Il-1β, Il-6, Tnf), histopathological changes (mucous degeneration, infiltration), and early disease biomarkers (e.g., Slc7a7 for MI, Kras for lung cancer). Mechanistically, SDF2L1 levels positively regulated O-mannosyltransferase content; Sdf2l1 deficiency reduced these enzymes and altered protein O-mannosylation, increasing TLR4 and MCM8 modifications/protein levels in vivo, while OE decreased them in vitro.

conclusionSDF2L1 exerts a complex modulatory role in oxLDL responses, linking ER stress, protein aggregation, and O-mannosylation to MI and lung cancer. Optimal SDF2L1 levels maintain homeostasis; deviations promote pathology, positioning SDF2L1 as a potential biomarker and therapeutic target for oxLDL-driven diseases.

Indexed as

Endoplasmic Reticulum StressLipoproteins, LDLLung NeoplasmsMyocardial InfarctionProtein Aggregation, PathologicalAnimalsEndoplasmic Reticulum Chaperone BiPHumansMiceMice, Inbred C57BLMice, KnockoutProteotoxic StressEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanHspa5 protein, mouseLipoproteins, LDLoxidized low density lipoproteinCardiovascular diseaseEndoplasmic reticulum stressLung cancerMCM8O-mannosylationO-mannosyltransferaseOxidized low-density lipoprotein (oxLDL)Protein aggregationSDF2L1Sdf2l1 knockout miceTLR4

Identifiers

PMID41781544
PMCPMC13003032

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.