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Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells

Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in os...

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Autores principales: Chang, Jia-Feng, Hsieh, Chih-Yu, Liou, Jian-Chiun, Liu, Shih-Hao, Hung, Chi-Feng, Lu, Kuo-Cheng, Lin, Chih-Cheng, Wu, Chang-Chin, Ka, Shuk-Man, Wen, Li-Li, Wu, Mai-Szu, Zheng, Cai-Mei, Ko, Wen-Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472002/
https://www.ncbi.nlm.nih.gov/pubmed/32722241
http://dx.doi.org/10.3390/toxins12080472
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author Chang, Jia-Feng
Hsieh, Chih-Yu
Liou, Jian-Chiun
Liu, Shih-Hao
Hung, Chi-Feng
Lu, Kuo-Cheng
Lin, Chih-Cheng
Wu, Chang-Chin
Ka, Shuk-Man
Wen, Li-Li
Wu, Mai-Szu
Zheng, Cai-Mei
Ko, Wen-Chin
author_facet Chang, Jia-Feng
Hsieh, Chih-Yu
Liou, Jian-Chiun
Liu, Shih-Hao
Hung, Chi-Feng
Lu, Kuo-Cheng
Lin, Chih-Cheng
Wu, Chang-Chin
Ka, Shuk-Man
Wen, Li-Li
Wu, Mai-Szu
Zheng, Cai-Mei
Ko, Wen-Chin
author_sort Chang, Jia-Feng
collection PubMed
description Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients.
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spelling pubmed-74720022020-09-17 Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells Chang, Jia-Feng Hsieh, Chih-Yu Liou, Jian-Chiun Liu, Shih-Hao Hung, Chi-Feng Lu, Kuo-Cheng Lin, Chih-Cheng Wu, Chang-Chin Ka, Shuk-Man Wen, Li-Li Wu, Mai-Szu Zheng, Cai-Mei Ko, Wen-Chin Toxins (Basel) Article Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients. MDPI 2020-07-24 /pmc/articles/PMC7472002/ /pubmed/32722241 http://dx.doi.org/10.3390/toxins12080472 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Jia-Feng
Hsieh, Chih-Yu
Liou, Jian-Chiun
Liu, Shih-Hao
Hung, Chi-Feng
Lu, Kuo-Cheng
Lin, Chih-Cheng
Wu, Chang-Chin
Ka, Shuk-Man
Wen, Li-Li
Wu, Mai-Szu
Zheng, Cai-Mei
Ko, Wen-Chin
Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title_full Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title_fullStr Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title_full_unstemmed Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title_short Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
title_sort scavenging intracellular ros attenuates p-cresyl sulfate-triggered osteogenesis through mapk signaling pathway and nf-κb activation in human arterial smooth muscle cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472002/
https://www.ncbi.nlm.nih.gov/pubmed/32722241
http://dx.doi.org/10.3390/toxins12080472
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