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EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway

Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to ha...

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Autores principales: Yang, Kaifan, Chen, Yanlin, Xiang, Xin, Lin, Yanling, Fei, Chengshuo, Chen, Zesen, Lai, Zhongming, Yu, Yongpeng, Tan, Ruiqian, Dong, Jiale, Zhang, Junxiong, Li, Peng, Wang, Liang, Zhang, Zhongmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515692/
https://www.ncbi.nlm.nih.gov/pubmed/36185336
http://dx.doi.org/10.7150/ijms.76077
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author Yang, Kaifan
Chen, Yanlin
Xiang, Xin
Lin, Yanling
Fei, Chengshuo
Chen, Zesen
Lai, Zhongming
Yu, Yongpeng
Tan, Ruiqian
Dong, Jiale
Zhang, Junxiong
Li, Peng
Wang, Liang
Zhang, Zhongmin
author_facet Yang, Kaifan
Chen, Yanlin
Xiang, Xin
Lin, Yanling
Fei, Chengshuo
Chen, Zesen
Lai, Zhongming
Yu, Yongpeng
Tan, Ruiqian
Dong, Jiale
Zhang, Junxiong
Li, Peng
Wang, Liang
Zhang, Zhongmin
author_sort Yang, Kaifan
collection PubMed
description Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism. Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-β1 (TGF-β1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-β1-neutralizing antibody. Results: The results showed that EGF, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-β1-neutralizing antibody. Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-β1/Smad3 signaling pathway, which eventually contributes to LFH.
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spelling pubmed-95156922022-09-29 EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway Yang, Kaifan Chen, Yanlin Xiang, Xin Lin, Yanling Fei, Chengshuo Chen, Zesen Lai, Zhongming Yu, Yongpeng Tan, Ruiqian Dong, Jiale Zhang, Junxiong Li, Peng Wang, Liang Zhang, Zhongmin Int J Med Sci Research Paper Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism. Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-β1 (TGF-β1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-β1-neutralizing antibody. Results: The results showed that EGF, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-β1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-β1-neutralizing antibody. Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-β1/Smad3 signaling pathway, which eventually contributes to LFH. Ivyspring International Publisher 2022-08-29 /pmc/articles/PMC9515692/ /pubmed/36185336 http://dx.doi.org/10.7150/ijms.76077 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Yang, Kaifan
Chen, Yanlin
Xiang, Xin
Lin, Yanling
Fei, Chengshuo
Chen, Zesen
Lai, Zhongming
Yu, Yongpeng
Tan, Ruiqian
Dong, Jiale
Zhang, Junxiong
Li, Peng
Wang, Liang
Zhang, Zhongmin
EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title_full EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title_fullStr EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title_full_unstemmed EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title_short EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway
title_sort egf contributes to hypertrophy of human ligamentum flavum via the tgf-β1/smad3 signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515692/
https://www.ncbi.nlm.nih.gov/pubmed/36185336
http://dx.doi.org/10.7150/ijms.76077
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