TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids

Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibr...

Full description

Saved in:
Bibliographic Details
Published in:Experimental dermatology 2022-10, Vol.31 (10), p.1533-1542
Main Authors: Feng, Qing‐Lan, Gu, Jing‐Jing, Chen, Jun‐Yi, Zheng, Wen‐Yue, Pan, Hui‐Hui, Xu, Xue‐Yan, Deng, Cheng‐Cheng, Yang, Bin
Format: Article
Language:English
Subjects:
Cell growth
Cell proliferation
Collagen
Collagen (type I)
Dermis
Extracellular matrix
fibroblast
Fibroblasts
IL6
Interleukin 6
Janus kinase 2
keloid
Signal transduction
Skin diseases
Skin lesions
Stat3 protein
Thrombospondin
TSP1
Wound healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.
ISSN:0906-6705
1600-0625
DOI:10.1111/exd.14623