Evidence mapPaperPMID 35044447Full record

ArticleDiabetes2022

Pathogenic Role of Diabetes-Induced Overexpression of Kallistatin in Corneal Wound Healing Deficiency Through Inhibition of Canonical Wnt Signaling.

Wentao Liang, Li Huang, Xiang Ma, Lijie Dong, Rui Cheng, Marcus Dehdarani, Dimitrios Karamichos, Jian-Xing Ma

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Targeting endothelial ERG to mitigate vascular regression in retinopathies.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Peroxisome proliferator-activated receptor-α (PPARα) regulates wound healing and mitochondrial metabolism in the cornea.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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

8 authors at 4 institutions in 2 countries.

Wentao LiangDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Li HuangDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Xiang MaDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Lijie DongDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Rui ChengDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Marcus DehdaraniDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Dimitrios KaramichosNorth Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX.
Jian-Xing MaDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.ORCID 0000-0001-8815-1716
University of Oklahoma Health Sciences Center · USFujian Medical University · CNTianjin Medical University Eye Hospital · CNUniversity of North Texas · US

Funding

STUDIES OF RPE65R01EY012231 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1998 to 2004
$1.0M
A Novel Pathogenic Pathway for Diabetic KeratopathyR01EY028949 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2024 to 2025
$758k
P30 Center Core Grant for Vision ResearchP30EY021725 · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2025 to 2025
$580k
A new pathogenic mechanism for diabetic retinopathyR01EY019309 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$474k
Studies of retinyl ester hydrolase in the visual cycleR01EY032930 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$388k
Dysregulation of Wnt signaling in subretinal fibrosis in AMDR01EY032931 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$388k
NEI NIH HHS P30 EY021725NEI NIH HHS R01 EY012231NEI NIH HHS R01 EY019309NEI NIH HHS R01 EY028949NEI NIH HHS R01 EY032930NEI NIH HHS R01 EY032931NIGMS NIH HHS P30 GM122744
6 · The paper itself

Abstract

It was reported previously that circulation levels of kallistatin, an endogenous Wnt signaling inhibitor, are increased in patients with diabetes. The current study was conducted to determine the role of kallistatin in delayed wound healing in diabetic corneas. Immunostaining and Western blot analysis showed kallistatin levels were upregulated in corneas from humans and rodents with diabetes. In murine corneal wound healing models, the canonical Wnt signaling was activated in nondiabetic corneas and suppressed in diabetic corneas, correlating with delayed wound healing. Transgenic expression of kallistatin suppressed the activation of Wnt signaling in the cornea and delayed wound healing. Local inhibition of Wnt signaling in the cornea by kallistatin, an LRP6-blocking antibody, or the soluble VLDL receptor ectodomain (an endogenous Wnt signaling inhibitor) delayed wound healing. In contrast, ablation of the VLDL receptor resulted in overactivation of Wnt/β-catenin signaling and accelerated corneal wound healing. Activation of Wnt signaling in the cornea accelerated wound healing. Activation of Wnt signaling promoted human corneal epithelial cell migration and proliferation, which was attenuated by kallistatin. Our findings suggested that diabetes-induced overexpression of kallistatin contributes to delayed corneal wound healing by inhibiting the canonical Wnt signaling. Thus, kallistatin and Wnt/β-catenin signaling in the cornea could be potential therapeutic targets for diabetic corneal complications.

Indexed as

Corneal InjuriesDiabetes ComplicationsDiabetes MellitusAnimalsbeta CateninCorneaHumansMiceSerpinsWnt Signaling PathwayWound Healingbeta CateninkallistatinSerpins

Identifiers

PMID35044447
PMCPMC8965664
OpenAlexW4206837213

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.