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Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway
Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinic reports indicate cigarette smoking is an independent risk factor for chronic kidney disease including DN; however, the underlying molecular mechanisms are not clear. Recent studies have demonstrated that nicotine, one of...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269139/ https://www.ncbi.nlm.nih.gov/pubmed/29572389 http://dx.doi.org/10.1042/BSR20180100 |
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author | Lan, Xiqian Wen, Hongxiu Aslam, Rukhsana Shoshtari, Seyedeh Shadafarin Marashi Mishra, Abheepsa Kumar, Vinod Wang, Haichao Wu, Guisheng Luo, Huairong Malhotra, Ashwani Singhal, Pravin C. |
author_facet | Lan, Xiqian Wen, Hongxiu Aslam, Rukhsana Shoshtari, Seyedeh Shadafarin Marashi Mishra, Abheepsa Kumar, Vinod Wang, Haichao Wu, Guisheng Luo, Huairong Malhotra, Ashwani Singhal, Pravin C. |
author_sort | Lan, Xiqian |
collection | PubMed |
description | Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinic reports indicate cigarette smoking is an independent risk factor for chronic kidney disease including DN; however, the underlying molecular mechanisms are not clear. Recent studies have demonstrated that nicotine, one of the active compounds in cigarette smoke, contributes to the pathogenesis of the cigarette smoking-accelerated chronic kidney disease. One of the characteristics of DN is the expansion of mesangium, a precursor of glomerular sclerosis. In the present study, we examined the involvement of Wnt/β-catenin pathway in nicotine-mediated mesangial cell growth in high glucose milieu. Primary human renal mesangial cells were treated with nicotine in the presence of normal (5 mM) or high glucose (30 mM) followed by evaluation for cell growth. In the presence of normal glucose, nicotine increased both the total cell numbers and Ki-67 positive cell ratio, indicating that nicotine stimulated mesangial cell proliferation. Although high glucose itself also stimulated mesangial cell proliferation, nicotine further enhanced the mitogenic effect of high glucose. Similarly, nicotine increased the expression of Wnts, β-catenin, and fibronectin in normal glucose medium, but further increased mesangial cell expression of these proteins in high glucose milieu. Pharmacological inhibition or genetic knockdown of β-catenin activity or expression with specific inhibitor FH535 or siRNA significantly impaired the nicotine/glucose-stimulated cell proliferation and fibronectin production. We conclude that nicotine may enhance renal mesangial cell proliferation and fibronectin production under high glucose milieus partly through activating Wnt/β-catenin pathway. Our study provides insight into molecular mechanisms involved in DN. |
format | Online Article Text |
id | pubmed-6269139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62691392018-12-13 Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway Lan, Xiqian Wen, Hongxiu Aslam, Rukhsana Shoshtari, Seyedeh Shadafarin Marashi Mishra, Abheepsa Kumar, Vinod Wang, Haichao Wu, Guisheng Luo, Huairong Malhotra, Ashwani Singhal, Pravin C. Biosci Rep Research Articles Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinic reports indicate cigarette smoking is an independent risk factor for chronic kidney disease including DN; however, the underlying molecular mechanisms are not clear. Recent studies have demonstrated that nicotine, one of the active compounds in cigarette smoke, contributes to the pathogenesis of the cigarette smoking-accelerated chronic kidney disease. One of the characteristics of DN is the expansion of mesangium, a precursor of glomerular sclerosis. In the present study, we examined the involvement of Wnt/β-catenin pathway in nicotine-mediated mesangial cell growth in high glucose milieu. Primary human renal mesangial cells were treated with nicotine in the presence of normal (5 mM) or high glucose (30 mM) followed by evaluation for cell growth. In the presence of normal glucose, nicotine increased both the total cell numbers and Ki-67 positive cell ratio, indicating that nicotine stimulated mesangial cell proliferation. Although high glucose itself also stimulated mesangial cell proliferation, nicotine further enhanced the mitogenic effect of high glucose. Similarly, nicotine increased the expression of Wnts, β-catenin, and fibronectin in normal glucose medium, but further increased mesangial cell expression of these proteins in high glucose milieu. Pharmacological inhibition or genetic knockdown of β-catenin activity or expression with specific inhibitor FH535 or siRNA significantly impaired the nicotine/glucose-stimulated cell proliferation and fibronectin production. We conclude that nicotine may enhance renal mesangial cell proliferation and fibronectin production under high glucose milieus partly through activating Wnt/β-catenin pathway. Our study provides insight into molecular mechanisms involved in DN. Portland Press Ltd. 2018-05-31 /pmc/articles/PMC6269139/ /pubmed/29572389 http://dx.doi.org/10.1042/BSR20180100 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Lan, Xiqian Wen, Hongxiu Aslam, Rukhsana Shoshtari, Seyedeh Shadafarin Marashi Mishra, Abheepsa Kumar, Vinod Wang, Haichao Wu, Guisheng Luo, Huairong Malhotra, Ashwani Singhal, Pravin C. Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title | Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title_full | Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title_fullStr | Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title_full_unstemmed | Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title_short | Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/β-catenin pathway |
title_sort | nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of wnt/β-catenin pathway |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269139/ https://www.ncbi.nlm.nih.gov/pubmed/29572389 http://dx.doi.org/10.1042/BSR20180100 |
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