SPARC activates p38γ signaling to promote PFKFB3 protein stabilization and contributes to keloid fibroblast

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Updated: Jun 9, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

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Yining Liu1, Wei Zhang2, Nan Lin2

  • 1Department of Burn and Plastic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266100, Shandong, People's Republic of China.

Inflammation and Regeneration
|November 1, 2024
PubMed
Abstract

Insights

Secreted protein acidic and cysteine rich (SPARC) promotes keloid progression by activating p38γ signaling, which stabilizes PFKFB3 and increases glycolysis in keloid fibroblasts. This finding offers new therapeutic targets for keloid treatment.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Biochemistry

Background:

  • Keloids are difficult to treat due to recurrence after surgery, impacting patient quality of life.
  • A lack of consensus on keloid treatment necessitates understanding underlying molecular mechanisms.
  • Investigating the role of secreted protein acidic and cysteine rich (SPARC) in keloid formation is crucial.

Purpose of the Study:

  • To explore the function of SPARC in keloid development.
  • To elucidate the molecular mechanisms by which SPARC influences keloid fibroblasts.
  • To identify potential therapeutic targets for keloid treatment.

Main Methods:

  • Assessed expression of SPARC, p38γ, PFKFB3, α-SMA, and Ki67 in keloid patients and mice models.
  • Utilized cell transfection, pharmacological inhibitors, and various assays (CCK-8, EdU, transwell, western blot) to study keloid fibroblast behavior.
  • Analyzed proliferation, migration, collagen production, and glycolysis in keloid fibroblasts.

Main Results:

  • SPARC, p38γ, and PFKFB3 were upregulated in keloids and fibrosis models.
  • SPARC enhanced keloid fibroblast proliferation, migration, and collagen production by inducing glycolysis.
  • SPARC activated p38γ signaling, stabilizing PFKFB3 expression and promoting keloid progression.

Conclusions:

  • SPARC activates the p38γ pathway, stabilizing PFKFB3 expression.
  • This mechanism promotes keloid fibroblast glycolysis and progression.
  • Targeting SPARC, p38γ, or PFKFB3 may offer new therapeutic strategies for keloids.
Keywords:
GlycolysisKeloidP38γPFKFB3SPARC

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