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Article Open Access

Regulatory role of POSTN in keloid pathogenesis

  • Authors:
    • Bin Jiang
    • Fan Zhuo
    • Xiahong Li
    • Kaoyuan Zhang
    • Jiaxu Gu
    • Jingwen Wu
    • Weilong Zhong
    • Yanfen Zou
    • Bo Yu
    • Cong Huang
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 337
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    Published online on: October 1, 2025
       https://doi.org/10.3892/mmr.2025.13701
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Abstract

Keloids are an inflammatory cutaneous condition, which are characterized by fibroproliferative overgrowth of the skin. Although keloids are not life‑threatening, their incidence and recurrence are relatively high, thus decreasing the quality of life of patients due to pain, pruritus and cosmetic reasons. Additionally, the precise molecular mechanisms underlying the pathogenesis of keloids remain largely unexplored, thus limiting the development of therapeutic interventions. To screen the key molecules in keloids, microarray data were selected from three different datasets obtained from the Gene Expression Omnibus database, namely GSE145725, GSE7890 and GSE44270. One differentially expressed gene was identified, periostin (POSTN), which was upregulated in keloid fibroblasts (KFs) compared with normal fibroblasts. Its high expression was further validated in KFs using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunofluorescence staining. Its potential function were explored in keloids through loss-of-function assay. Notably, the EdU incorporation assay and cell cycle assay indicated that POSTN knockdown had limited effects on the proliferation of KFs; however, the RT‑qPCR, western blotting, and RNA sequencing results suggested that POSTN inhibition blocked the JAK‑STAT signaling pathway and decreased the expression levels of various proinflammatory factors in KFs. Additionally, the RT‑qPCR and western blotting results demonstrated that IL‑4 and IL‑13, two significant mediators of T helper 2 (Th2) signaling, could induce POSTN expression in KFs. Notably, IL‑4 receptor (IL‑4R), a receptor for both IL‑4 and IL‑13, could be positively modulated by POSTN through the Reactome enrichment, RT‑qPCR and western blotting analysis. Furthermore, IL‑4R was essential for IL‑4/IL‑13‑induced POSTN upregulation in KFs, thus indicating a positive feedback loop between POSTN and Th2 signaling. Overall, the current study uncovered a novel mechanism of POSTN, which could be associated with keloid inflammation, thus highlighting the POSTN/Th2 feedback loop as a potential therapeutic target for patients with keloids. 
View Figures

Figure 1

POSTN is upregulated in KFs. (A) Venn
plot of common upregulated differentially expressed genes
identified from three independent datasets. (B) Relative mRNA
expression levels of POSTN in the three datasets. (C) Relative mRNA
expression levels of POSTN in KFs (n=3) and NFs derived from
healthy donors (n=3). (D) Representative western blotting and
semi-quantification of POSTN protein expression in KFs and NFs
(n=3/group). Data are presented as the mean ± SEM. ***P<0.001,
*P<0.05. KFs, keloid fibroblasts; NFs, normal fibroblasts;
POSTN, periostin.

Figure 2

Knockdown of POSTN shows limited
effects on the proliferation of KFs. (A) mRNA expression levels of
POSTN in KFs transfected with si-POSTN; mRNA levels were analyzed
using reverse transcription-quantitative PCR (n=4), whereas protein
levels were detected by western blotting. (B) CCK-8 assay revealed
that the proliferation was comparable between KFs transfected with
si-POSTN and si-CTL (n=4). (C) EdU staining of KFs transfected with
si-POSTN/si-CTL and their relative proliferation rate (n=5). Scale
bar: 50 µm. (D) Cell cycle progression was assessed using flow
cytometry after siRNA transfection, and the percentages of cells in
different phases were calculated (n=3). (E) mRNA expression levels
of cell cycle-related genes in KFs transfected with si-POSTN/si-CTL
(n=3). (F) mRNA expression levels of cell growth-related genes in
KFs transfected with si-POSTN/si-CTL (n=3). Data are presented as
the mean ± SEM. ***P<0.001, NS, not significant; POSTN,
periostin; si, small interfering.

Figure 3

Knockdown of POSTN blocks the
JAK-STAT signaling pathway in KFs. (A) JAK-STAT pathway was
revealed to be associated with POSTN knockdown in KFs by gene set
enrichment analysis. (B) Heatmap showing DEGs related to the
JAK-STAT pathway in si-POSTN and si-CTL KFs. Three independent
RNA-sequencing experiments are shown in each group. (C) Reverse
transcription-quantitative PCR analysis was performed to validate
the DEGs related to the JAK-STAT pathway in si-POSTN- and
si-CTL-transfected KFs (n=3). (D) Representative western blotting
and semi-quantification of the protein levels of p-STAT1 (Tyr701)
and p-STAT1 (Ser727) in KFs transfected with si-POSTN and si-CTL in
the presence or absence of IFNα +β treatment (n=3). Data are
presented as the mean ± SEM. ***P<0.001, **P<0.01,
*P<0.05. DEGs, differentially expressed genes; KFs, keloid
fibroblasts; NS, not significant; p-, phosphorylated; POSTN,
periostin; si, small interfering.

Figure 4

Knockdown of POSTN decreases the
expression of proinflammatory factors in KFs. (A) Cytokine-cytokine
receptor interaction pathway was revealed to be associated with
POSTN knockdown in KFs by gene set enrichment analysis. (B) Heatmap
showing DEGs related to cytokine-cytokine receptor interaction in
si-POSTN and si-CTL KFs. The red box highlights the downregulated
expression of IL-4R in si-POSTN KFs compared with si-CTL KFs. Three
independent RNA-sequencing experiments are shown in each group. (C)
Reverse transcription-quantitative PCR was performed to validate
the DEGs related to cytokine-cytokine receptor interaction in
si-POSTN- and si-CTL-transfected KFs (n=4). KF#1 and KF#2 indicate
KFs derived from two different patients. ***P<0.001,
**P<0.01, *P<0.05. DEGs, differentially expressed genes; NES,
normalized enrichment score; IL-4R, IL-4 receptor; KFs, keloid
fibroblasts; POSTN, periostin; si, small interfering.

Figure 5

Expression of POSTN is upregulated by
IL-4 and/or IL-13 in KFs. (A) Reverse transcription-quantitative
PCR results revealed that IL-4 and IL-13 increased the mRNA
expression levels of POSTN in NFs and KFs derived from different
donors (n=4/group). (B) Western blotting showed that IL-4 and/or
IL-13 induced the protein expression of POSTN in KFs derived from
two different patients with keloids. (C) Immunofluorescence
staining of the protein expression of POSTN in KFs in the presence
or absence of IL-4 or IL-13 stimulation. Data are presented as the
mean ± SEM. ***P<0.001 vs. CTL. KFs, keloid fibroblasts; NFs,
normal fibroblasts; POSTN, periostin

Figure 6

IL-4R is positively regulated by
POSTN and essential for IL-4/IL-13-induced POSTN upregulation in
KFs. (A) A bubble chart showing the top 20 signaling pathways
associated with POSTN in KFs based on Reactome analysis. The IL-4
and 13 signaling pathway is highlighted in red. (B) RT-qPCR results
showing the mRNA expression levels of POSTN and IL-4R in KFs
transfected with si-POSTN/si-CTL (n=4). (C) Western blotting of the
protein expression of POSTN and IL-4R in KFs transfected with
si-POSTN/si-CTL. (D) RT-qPCR results showing the mRNA expression
levels of POSTN in KFs transfected with si-IL-4R/si-CTL, in the
presence or absence of IL-4/IL-13 treatment (n=4). (E)
Representative blots showing protein expression of POSTN in KFs
transfected with si-IL-4R/si-CTL, in the presence or absence of
IL-4/IL-13 treatment. (F) Immunofluorescence staining showing
protein expression of POSTN in KFs transfected with
si-IL-4R/si-CTL, in the presence or absence of IL-4/IL-13
treatment. Data are presented as the mean ± SEM. ***P<0.001,
*P<0.05. IL-4R, IL-4 receptor; KFs, keloid fibroblasts; POSTN,
periostin; RT-qPCR, reverse transcription-quantitative PCR; si,
small interfering.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang B, Zhuo F, Li X, Zhang K, Gu J, Wu J, Zhong W, Zou Y, Yu B, Huang C, Huang C, et al: Regulatory role of POSTN in keloid pathogenesis. Mol Med Rep 32: 337, 2025.
APA
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J. ... Huang, C. (2025). Regulatory role of POSTN in keloid pathogenesis. Molecular Medicine Reports, 32, 337. https://doi.org/10.3892/mmr.2025.13701
MLA
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J., Zhong, W., Zou, Y., Yu, B., Huang, C."Regulatory role of POSTN in keloid pathogenesis". Molecular Medicine Reports 32.6 (2025): 337.
Chicago
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J., Zhong, W., Zou, Y., Yu, B., Huang, C."Regulatory role of POSTN in keloid pathogenesis". Molecular Medicine Reports 32, no. 6 (2025): 337. https://doi.org/10.3892/mmr.2025.13701
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang B, Zhuo F, Li X, Zhang K, Gu J, Wu J, Zhong W, Zou Y, Yu B, Huang C, Huang C, et al: Regulatory role of POSTN in keloid pathogenesis. Mol Med Rep 32: 337, 2025.
APA
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J. ... Huang, C. (2025). Regulatory role of POSTN in keloid pathogenesis. Molecular Medicine Reports, 32, 337. https://doi.org/10.3892/mmr.2025.13701
MLA
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J., Zhong, W., Zou, Y., Yu, B., Huang, C."Regulatory role of POSTN in keloid pathogenesis". Molecular Medicine Reports 32.6 (2025): 337.
Chicago
Jiang, B., Zhuo, F., Li, X., Zhang, K., Gu, J., Wu, J., Zhong, W., Zou, Y., Yu, B., Huang, C."Regulatory role of POSTN in keloid pathogenesis". Molecular Medicine Reports 32, no. 6 (2025): 337. https://doi.org/10.3892/mmr.2025.13701
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