Highlights
- •SPARC expression is upregulated in keloid skin tissues.
- •SPARC promotes the proliferation and migration of keloid fibroblasts.
- •SPARC promotes the collagen production and ECM synthesis in fibroblasts.
- •SPARC inhibits the activation of p53 signaling in fibroblasts.
Abstract
Background
Keloid, an aggressive fibroproliferative disease of the skin, is usually caused by
infectious skin diseases, burns, and trauma.
Objective
This study aimed to assess the effect of SPARC on the keloid pathogenesis.
Methods
In normal skin and keloid scar tissues, changes in SPARC expression were analysed
by qRT-PCR, western blotting, and immunohistochemistry. Keloid fibroblasts were isolated
from human keloid tissue. GSEA was performed to investigate the signalling pathways
related to SPARC. Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine, transwell assay,
and scratching assays were used to assess fibroblast proliferation and migration.
Changes in α-SMA, fibronectin, collagen I, and collagen III levels were examined in
fibroblasts by western blotting.
Results
SPARC expression was upregulated in keloid scar tissues. In fibroblasts, cell proliferation,
migration, collagen production, and extracellular matrix (ECM) synthesis were promoted
by SPARC overexpression, whereas SPARC knockdown resulted a converse result. GSEA
showed that SPARC regulates the p53 pathway. In keloid scar tissues, there was a negative
correlation between SPARC and p53 expression. p53 expression was decreased by SPARC
overexpression, whereas SPARC knockdown increased p53 expression. Furthermore, the
effects of SPARC on the fibroblast phenotype were reversed by p53 overexpression.
Conclusions
Fibroblast proliferation, migration, and ECM synthesis were promoted by SPARC overexpression,
which was achieved by regulating the p53 pathway. Our findings provide new therapeutic
targets for keloids.
Keywords
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Article info
Publication history
Published online: January 07, 2023
Accepted:
January 4,
2023
Received in revised form:
December 20,
2022
Received:
October 14,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
