Evidence map›Paper›PMID 41533912›Full record

ArticleInvestigative ophthalmology & visual science2026

CGRP/TSP1 Signaling Dampens Corneal Inflammation and Fibrosis by Targeting A2M During Corneal Stromal Wound Healing.

Hongqi Ge, Yangyang Zhang, Qian Guo, Ya Li, Lingling Yang, Xinyi Zang, Jin Xie, Yao Wang, Yizhou Li, Xia Qi and 3 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Hongqi GeEye Institute of Shandong First Medical University, Qingdao, China.
Yangyang ZhangQingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
Qian GuoEye Institute of Shandong First Medical University, Qingdao, China.
Ya LiEye Institute of Shandong First Medical University, Qingdao, China.
Lingling YangEye Institute of Shandong First Medical University, Qingdao, China.
Xinyi ZangQingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
Jin XieQingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
Yao WangEye Institute of Shandong First Medical University, Qingdao, China.
Yizhou LiEye Institute of Shandong First Medical University, Qingdao, China.
Xia QiEye Institute of Shandong First Medical University, Qingdao, China.
Yalin WangShandong Freda Pharmaceutical Group Co., Ltd., Jinan, China.
Qingjun ZhouEye Institute of Shandong First Medical University, Qingdao, China.
Xiaolei WangEye Institute of Shandong First Medical University, Qingdao, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: To investigate the specific role of thrombospondin-1 (TSP1), encoded by the Thbs1 gene, in corneal stromal wound healing and to elucidate its underlying mechanism. Methods: A corneal stromal injury model was established by removing the epithelium and superficial stroma. We assessed Thbs1 expression using single-cell sequencing and compared the corneal healing responses between wild-type and Thbs1-deficient (Thbs1-/-) mice. Bulk RNA sequencing was conducted to identify key downstream targets of Thbs1. The regulation of TSP1 by calcitonin gene-related peptide (CGRP) was investigated through intervening CGRP signaling in human telomerase-immortalized keratocytes and murine corneas. Results: Thbs1 was highly expressed in corneal stroma and upregulated following injury. Thbs1-/- mice exhibited more severe corneal lesions than wild-type controls, with elevated corneal opacity scores and augmented inflammation and fibrosis markers. Transcriptomic analysis identified A2m (encoding α2-macroglobulin [A2M]) as a key downstream target of Thbs1. A2m expression also increased after injury, peaking later than Thbs1. Topical depletion of A2m in wild-type mice recapitulated the exacerbated corneal phenotype observed in Thbs1-/- mice. Exogenous CGRP robustly induced both TSP1 and A2M expression in vitro and in vivo, but the CGRP receptor antagonist BIBN4096 suppressed their expression and concurrently exacerbated corneal lesions. TSP1 and A2M were similarly upregulated in patients with corneal scarring from alkali burn or fungal infection. Conclusions: Our findings indicate that TSP1 and A2M induction represents a conserved stress-protective response to corneal stromal injury. The CGRP/TSP1/A2M signaling axis is critical for modulating stromal inflammation and fibrosis, highlighting its therapeutic potential for enhancing corneal stromal repair.

Indexed as

Calcitonin Gene-Related PeptideCorneal InjuriesCorneal StromaGene Expression RegulationThrombospondin 1Wound HealingAnimalsDisease Models, AnimalFibrosisHumansInflammationMiceMice, Inbred C57BLMice, KnockoutSignal TransductionCalcitonin Gene-Related PeptideThbs1 protein, mouseThrombospondin 1

Identifiers

PMID41533912
PMCPMC12798754

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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.