Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-β1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation.

Szu-Yuan Wu,Guo-Yu Tsai,Yu-Ting Chen,Fu-Yin Hsu,Pai-An Hwang

doi:10.3390/md18030136

Abstract

Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-β1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-β1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.

Highlights

Radiotherapy (RT) is widely used to treat various cancers; RT can cause varying degrees of damage to different tissues and organs, including the skin, ligaments, tendons, muscles, viscera, nerves, lungs, gastrointestinal and genitourinary tracts, and bone, depending on the treatment site [1].Radiation-induced fibrosis (RIF) may be caused by previous acute inflammation and result in long-term disability following RT [2]
Fucoidan enhances the proliferation of NIH3T3 fibroblasts [29], which may be because fucoidan can significantly of of cyclin
On radiation-induced fibrosis through TGF-β1/Smad pathway. These findings suggest that low-molecular-weight fucoidan (LMF) can. These findings suggest that LMF can suppress or reverse fibrosis in irradiated cells by inhibiting suppress or reverse fibrosis in irradiated cells by inhibiting fibroblast contractility and collagen I

Summary

Introduction

Radiation-induced fibrosis (RIF) may be caused by previous acute inflammation and result in long-term disability following RT [2]. Growth factors, fibroblast proliferation and differentiation, and excessive production and deposition of extracellular matrix proteins and collagen are involved in RIF [3]. Herskind et al [4] reported that the cellular response to radiation injury results in an altered differentiation pattern of the fibroblast/fibrocyte cell system, and RT accelerates. Mar. Drugs 2020, 18, 136; doi:10.3390/md18030136 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2020, 18, 136 the differentiation of mitotic progenitor fibroblasts to postmitotic functional fibrocytes, resulting in the synthesis of extracellular matrix proteins, such as interstitial collagen. Yano et al [5]

Methods

Results

Conclusion