ArticleBiology direct2026
HIF-1α/NREP axis promotes hypertrophic scar fibroblast proliferation and collagen deposition via activation of the TGF-β1/Smad pathway.
Article in Biology direct, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
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.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypertrophic scar (HS) is a fibroproliferative skin disorder characterized by excessive fibroblast proliferation and collagen overproduction during aberrant wound healing. Although hypoxia is a well-recognized driver of HS formation, the molecular mechanisms linking hypoxic signaling to fibroblast activation remain incompletely understood.
methodsIn this study, the expression of hypoxia-inducible factor 1α (HIF-1α), neuronal regeneration-related protein (NREP), and phosphorylated small mother against decapentaplegic family member 2/3 (p-Smad2/3) was examined in HS and matched normal tissues from patients. Hypertrophic scar fibroblasts (HSFBs) were cultured under hypoxic or normoxic conditions, followed by genetic manipulation of HIF-1α or NREP to assess their effects on fibroblast proliferation and collagen synthesis. The direct transcriptional regulation of NREP by HIF-1α was confirmed using dual-luciferase reporter and ChIP assays.
resultsCompared with normal tissues, HS tissues exhibited markedly elevated expression of HIF-1α, NREP, and phosphorylated Smad2/3. Hypoxia significantly increased HIF-1α and NREP levels in HSFBs, promoting fibroblast proliferation and collagen deposition, whereas knockdown of either HIF-1α or NREP abrogated these effects. Mechanistically, HIF-1α directly bound to the NREP promoter to enhance its transcription, and NREP overexpression partially rescued the suppressive effects of HIF-1α knockdown. Furthermore, HIF-1α-induced NREP upregulation activated the TGF-β1/Smad signaling cascade, while inhibition of this cascade counteracted the effect of NREP overexpression on the changes caused by HIF-1α silencing.
conclusionOur findings identify a novel HIF-1α/NREP/TGF-β1-Smad axis that drives fibroblast hyperproliferation and excessive collagen accumulation in HS. Targeting this signaling pathway may offer a promising therapeutic strategy for preventing or treating HS formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.