Dataset Information

Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post?laminectomy.

ABSTRACT: Epidural fibrosis (EF)?induced failed back surgery syndrome (FBSS) in patients post?laminectomy remains a medical challenge. Although the scarring mechanisms remain unclear, the majority of aetiological studies have reported fibroblast dysfunction. Honokiol, the major bioactive constituent of the magnolia tree, exerts a variety of pharmacological effects, including anti?proliferative and anti?fibrotic effects, on various cell types. The present study investigated whether honokiol attenuates EF progression. In vitro, it was found that honokiol inhibited excessive fibroblast proliferation induced by transforming growth factor??1 (TGF??1) and the synthesis of extracellular matrix (ECM) components, including fibronectin and type I collagen, in a dose?dependent manner. These effects were attributed to the ability of honokiol to suppress the activity of connective tissue growth factor (CTGF), which is indispensable for the progression of fibrosis. Mechanistically, honokiol attenuated the TGF??1?induced activation of the Smad2/3 and mitogen?activated protein kinase (MAPK) signalling pathways in fibroblasts. In vivo, honokiol reduced the proliferation of fibroblasts and the synthesis of ECM components, thus ameliorating EF in a rat model post?laminectomy. Taken together, these preclinical findings suggest that honokiol deserves further consideration as a candidate therapeutic agent for EF.

SUBMITTER: Xu D

PROVIDER: S-EPMC7595651 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post‑laminectomy.

Xu Daoliang D Zeng Weimin W Han Xuyao X Qian Tianchen T Sun Jingyu J Qi Fangzhou F Liu Chen C Wang Quan Q Jin Haiming H

International journal of molecular medicine 20201022 6

Epidural fibrosis (EF)‑induced failed back surgery syndrome (FBSS) in patients post‑laminectomy remains a medical challenge. Although the scarring mechanisms remain unclear, the majority of aetiological studies have reported fibroblast dysfunction. Honokiol, the major bioactive constituent of the magnolia tree, exerts a variety of pharmacological effects, including anti‑proliferative and anti‑fibrotic effects, on various cell types. The present study investigated whether honokiol attenuates EF p ...[more]

PMID: 33125121

Similar Datasets

Project description:Maintaining a balanced state in remodeling the extracellular matrix is crucial for tissue homeostasis, and this process is altered during skin cancer progression. In melanoma, several proteolytic enzymes are expressed in a time and compartmentalized manner to support tumor progression by generating a permissive environment. One of these proteases is the matrix metalloproteinase 14 (MMP14). We could previously show that deletion of MMP14 in dermal fibroblasts results in the generation of a fibrotic-like skin in which melanoma growth is impaired. That was primarily due to collagen I accumulation due to lack of the collagenolytic activity of MMP14. However, as well as collagen I processing, MMP14 can also process several extracellular matrices. We investigated extracellular matrix alterations occurring in the MMP14-deleted fibroblasts that can contribute to the modulation of melanoma growth. The matrix deposited by cultured MMP14-deleted fibroblast displayed an antiproliferative and anti-migratory effect on melanoma cells in vitro. Analysis of the secreted and deposited-decellularized fibroblast's matrix identified a few altered proteins, among which the most significantly changed was collagen XIV. This collagen was increased because of post-translational events, while de novo synthesis was unchanged. Collagen XIV as a substrate was not pro-proliferative, pro-migratory, or adhesive, suggesting a negative regulatory role on melanoma cells. Consistent with that, increasing collagen XIV concentration in wild-type fibroblast-matrix led to reduced melanoma proliferation, migration, and adhesion. In support of its anti-tumor activity, enhanced accumulation of collagen XIV was detected in peritumoral areas of melanoma grown in mice with the fibroblast's deletion of MMP14. In advanced human melanoma samples, we detected reduced expression of collagen XIV compared to benign nevi, which showed a robust expression of this molecule around melanocytic nests. This study shows that loss of fibroblast-MMP14 affects melanoma growth through altering the peritumoral extracellular matrix (ECM) composition, with collagen XIV being a modulator of melanoma progression and a new proteolytic substrate to MMP14.

Dataset Information

Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post?laminectomy.

Publications

Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post‑laminectomy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets