Evidence mapPaperPMID 40038579Full record

ArticleCellular & molecular biology letters2025

KLF5 enhances CXCL12 transcription in adipose-derived stem cells to promote endothelial progenitor cells neovascularization and accelerate diabetic wound healing.

Yunjia Xie, Xuejun Ni, Xiaofen Wan, Nating Xu, Lu Chen, Chensheng Lin, Xi Zheng, Beichen Cai, Qian Lin, Ruonan Ke and 4 more

Abstract read
In one paragraph

Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

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

9 citing papers 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

14 authors.

Yunjia Xie *Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Xuejun Ni *Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Xiaofen Wan *Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Nating XuDepartment of Burn and Plastic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, China.
Lu ChenDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Chensheng LinFujian Key Laboratory of Developmental and Neural Biology & Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, Fujian, China.
Xi ZhengFujian Key Laboratory of Developmental and Neural Biology & Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, Fujian, China.
Beichen CaiDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Qian LinDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Ruonan KeDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Tao HuangDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Xuefeng HuFujian Key Laboratory of Developmental and Neural Biology & Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, Fujian, China. Bioxfh@fjnu.edu.cn.
Biao WangDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China. biaowang@fjmu.edu.cn.ORCID http://orcid.org/0000-0001-6253-2713
Xiuying ShanDepartment of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China. xiuyingshan@fjmu.edu.cn.

Funding

Joint Funds for the Innovation of Science and Technology, Fujian Province No.2021Y9155Natural Science Foundation of Fujian Province No. 2021J01244Young and Middle-aged Key Personnel Training Project of Fujian Provincial Health Commission No.BPB-2024SXY
6 · The paper itself

Abstract

backgroundAdipose-derived stem cells (ADSCs) have been shown to accelerate diabetic wound healing by promoting neovascularization, though the underlying mechanisms are not fully understood. This study aims to explore whether ADSCs influence endothelial progenitor cells (EPCs) function to enhance diabetic wound healing.

methodsHuman adipose-derived stem cells (hADSCs) were isolated from patient adipose tissue and cultured under normal and high glucose (HG) conditions. RNA sequencing analyzed gene expression, while immunofluorescence validated findings in patient wound tissues. Mouse adipose-derived stem cells (ADSCs) from C57BL/6 mice were evaluated in vitro for their effects on EPCs under HG using EdU, Transwell, and tube formation assays. A diabetic mouse wound model was used to assess ADSCs therapeutic effects via digital imaging, histology, and immunofluorescence. Kruppel-like factor 5 (KLF5), identified via the JASPAR database, was confirmed by immunohistochemistry and immunofluorescence. KLF5 and C-X-C motif chemokine 12 (CXCL12) expression levels were measured by enzyme-linked immunosorbent assay (ELISA), western blot, and quantitative reverse transcription polymerase chain reaction (RT-qPCR), and their relationship was validated through dual-luciferase assays.

resultsWe constructed a neovascularization-related signature (NRS) comprising 75 genes on the basis of differentially expressed genes (DEGs) linked to neovascularization. GO and KEGG analyses revealed that the NRS is primarily involved in vasculature development and receptor-ligand activity. Seven hub genes (CD34, CXCL12, FGF7, FGF18, FGF1, TEK, KIT) were identified and validated. In a diabetic mouse model, CXCL12 knockdown in ADSCs reduced their ability of promoting wound healing and neovascularization. KLF5 expression was lower in patients with diabetic ulcers and diabetic mice wound tissues compared with normal tissues, while ADSCs treatment significantly increased KLF5 expression in diabetic mice wounds. Dual-luciferase reporter assays confirmed KLF5 as an upstream transcription factor of CXCL12. Additionally, knocking down KLF5 in ADSCs impaired their therapeutic effects on diabetic wound healing. In vitro, the addition of exogenous CXCL12 recombinant protein restored EPCs proliferation, migration, and vasculogenic capacity in a high glucose environment after KLF5 silencing in ADSCs.

conclusionsOur findings underscore the pivotal role of KLF5 in enhancing CXCL12 transcription within ADSCs, thereby facilitating EPC-mediated neovascularization and improving diabetic wound healing. Additionally, KLF5 emerges as a promising therapeutic target for accelerating tissue repair in diabetic wounds.

Indexed as

Adipose TissueChemokine CXCL12Endothelial Progenitor CellsKruppel-Like Transcription FactorsNeovascularization, PhysiologicWound HealingAnimalsCells, CulturedDiabetes Mellitus, ExperimentalHumansMaleMiceMice, Inbred C57BLStem CellsTranscription, GeneticChemokine CXCL12KLF5 protein, humanKruppel-Like Transcription FactorsAdipose-derived stem cellsDiabetic woundEndothelial progenitor cellsNeovascularizationWound healing

Identifiers

PMID40038579
PMCPMC11877965

What Socratic holds

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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 Socratic graph.