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IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells
The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of gl...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5280875/ https://www.ncbi.nlm.nih.gov/pubmed/28149534 http://dx.doi.org/10.1038/cddiscovery.2016.107 |
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author | Wu, Xinghuo Song, Yu Liu, Wei Wang, Kun Gao, Yong Li, Shuai Duan, Zhenfeng Shao, Zengwu Yang, Shuhua Yang, Cao |
author_facet | Wu, Xinghuo Song, Yu Liu, Wei Wang, Kun Gao, Yong Li, Shuai Duan, Zhenfeng Shao, Zengwu Yang, Shuhua Yang, Cao |
author_sort | Wu, Xinghuo |
collection | PubMed |
description | The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of glucose and oxygen. Islet amyloid polypeptide (IAPP) exerts its biological effects by regulating glucose metabolism. The purpose of this study was to investigate the expression of IAPP in degenerated IVD tissue, and IAPP modulation of ECM metabolism in human NP cells, especially the crosstalk mechanism between apoptosis and autophagy in these cells. We found that the expression of IAPP and Calcr-RAMP decreased considerably during IDD progression, along with the decrease in the expression of AG, BG, and Col2A1. Induction of IAPP in NP cells by transfection with pLV-IAPP enhanced the synthesis of aggrecan and Col2A1 and attenuated the expression of pro-inflammatory factors, tumor necrosis factor (TNF)-α, and interleukin (IL)-1. Upregulation of IAPP also affected the expression of the catabolic markers—matrix metalloproteinases (MMPs) 3, 9 and 13 and ADAMTS 4 and 5. Downregulation of IAPP by siRNA inhibited the expression of anabolic genes but increased the expression of catabolic genes and inflammatory factors. The expressions of autophagic and apoptotic markers in NP cells transfected with pLV-IAPP were upregulated, including BECLIN1, ATG5, ATG7, LC3 II/I and Bcl-2, while significantly increase in the expression of Bax and Caspase-3 in NP cells transfected with pLV-siIAPP. Mechanistically, PI3K/AKT-mTOR and p38/JNK MAPK signal pathways were involved. We propose that IAPP might play a pivotal role in the development of IDD, by regulating ECM metabolism and controlling the crosstalk between apoptosis and autophagy in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. |
format | Online Article Text |
id | pubmed-5280875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52808752017-02-01 IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells Wu, Xinghuo Song, Yu Liu, Wei Wang, Kun Gao, Yong Li, Shuai Duan, Zhenfeng Shao, Zengwu Yang, Shuhua Yang, Cao Cell Death Discov Article The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of glucose and oxygen. Islet amyloid polypeptide (IAPP) exerts its biological effects by regulating glucose metabolism. The purpose of this study was to investigate the expression of IAPP in degenerated IVD tissue, and IAPP modulation of ECM metabolism in human NP cells, especially the crosstalk mechanism between apoptosis and autophagy in these cells. We found that the expression of IAPP and Calcr-RAMP decreased considerably during IDD progression, along with the decrease in the expression of AG, BG, and Col2A1. Induction of IAPP in NP cells by transfection with pLV-IAPP enhanced the synthesis of aggrecan and Col2A1 and attenuated the expression of pro-inflammatory factors, tumor necrosis factor (TNF)-α, and interleukin (IL)-1. Upregulation of IAPP also affected the expression of the catabolic markers—matrix metalloproteinases (MMPs) 3, 9 and 13 and ADAMTS 4 and 5. Downregulation of IAPP by siRNA inhibited the expression of anabolic genes but increased the expression of catabolic genes and inflammatory factors. The expressions of autophagic and apoptotic markers in NP cells transfected with pLV-IAPP were upregulated, including BECLIN1, ATG5, ATG7, LC3 II/I and Bcl-2, while significantly increase in the expression of Bax and Caspase-3 in NP cells transfected with pLV-siIAPP. Mechanistically, PI3K/AKT-mTOR and p38/JNK MAPK signal pathways were involved. We propose that IAPP might play a pivotal role in the development of IDD, by regulating ECM metabolism and controlling the crosstalk between apoptosis and autophagy in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. Nature Publishing Group 2017-01-30 /pmc/articles/PMC5280875/ /pubmed/28149534 http://dx.doi.org/10.1038/cddiscovery.2016.107 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wu, Xinghuo Song, Yu Liu, Wei Wang, Kun Gao, Yong Li, Shuai Duan, Zhenfeng Shao, Zengwu Yang, Shuhua Yang, Cao IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title | IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title_full | IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title_fullStr | IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title_full_unstemmed | IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title_short | IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
title_sort | iapp modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5280875/ https://www.ncbi.nlm.nih.gov/pubmed/28149534 http://dx.doi.org/10.1038/cddiscovery.2016.107 |
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