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Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis

CD38 is a multifunctional protein involving in a number of signalling pathways. Given that the lack of CD38 is considered as a dedifferentiation marker of lymphocytes and other cells, we hypothesized that CD38 and its signalling pathway may participate in the epithelial-to-mesenchymal transition (EM...

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Autores principales: Boini, Krishna M, Xia, Min, Xiong, Jing, Li, Caixia, Payne, Lori P, Li, Pin-Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270217/
https://www.ncbi.nlm.nih.gov/pubmed/21992601
http://dx.doi.org/10.1111/j.1582-4934.2011.01462.x
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author Boini, Krishna M
Xia, Min
Xiong, Jing
Li, Caixia
Payne, Lori P
Li, Pin-Lan
author_facet Boini, Krishna M
Xia, Min
Xiong, Jing
Li, Caixia
Payne, Lori P
Li, Pin-Lan
author_sort Boini, Krishna M
collection PubMed
description CD38 is a multifunctional protein involving in a number of signalling pathways. Given that the lack of CD38 is considered as a dedifferentiation marker of lymphocytes and other cells, we hypothesized that CD38 and its signalling pathway may participate in the epithelial-to-mesenchymal transition (EMT) process of podocytes and thereby regulates the integrity of glomerular structure and function. Western blot analysis and RT-PCR demonstrated that renal tissue CD38 expression was lacking in CD38(−/−) mice or substantially reduced in renal CD38 shRNA-transfected WT (CD38-shRNA) mice compared to CD38(+/+) littermates. Confocal fluorescent microscopy demonstrated the reduced expression of epithelial markers (P-Cadherin, ZO-1 and podocin) and increased expression of mesenchymal markers (FSP-1, α-SMA and desmin) in the glomeruli of CD38(−/−) and CD38-shRNA mice compared to CD38(+/+) mice. Morphological examinations showed profound injury in the glomeruli of CD38(−/−) or CD38-shRNA mice compared to CD38(+/+) mice. This enhanced glomerular injury in CD38(−/−) or CD38-shRNA mice was accompanied by increased albuminuria and proteinuria. DOCA/high salt treatment further decreased the expression of epithelial markers and increased the abundance of mesenchymal markers, which were accompanied by more increased glomerular damage index and mean arterial pressure in CD38(−/−) and CD38-shRNA mice than CD38(+/+) mice. In vitro studies showed that inhibition of CD38 enhances the EMT in podocytes. In conclusion, our observations reveal that the normal expression of CD38 importantly contributes to the differentiation and function of podocytes and the defect of this gene expression may be a critical mechanism inducing EMT and consequently resulting in glomerular injury and sclerosis.
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spelling pubmed-32702172013-08-01 Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis Boini, Krishna M Xia, Min Xiong, Jing Li, Caixia Payne, Lori P Li, Pin-Lan J Cell Mol Med Original Articles CD38 is a multifunctional protein involving in a number of signalling pathways. Given that the lack of CD38 is considered as a dedifferentiation marker of lymphocytes and other cells, we hypothesized that CD38 and its signalling pathway may participate in the epithelial-to-mesenchymal transition (EMT) process of podocytes and thereby regulates the integrity of glomerular structure and function. Western blot analysis and RT-PCR demonstrated that renal tissue CD38 expression was lacking in CD38(−/−) mice or substantially reduced in renal CD38 shRNA-transfected WT (CD38-shRNA) mice compared to CD38(+/+) littermates. Confocal fluorescent microscopy demonstrated the reduced expression of epithelial markers (P-Cadherin, ZO-1 and podocin) and increased expression of mesenchymal markers (FSP-1, α-SMA and desmin) in the glomeruli of CD38(−/−) and CD38-shRNA mice compared to CD38(+/+) mice. Morphological examinations showed profound injury in the glomeruli of CD38(−/−) or CD38-shRNA mice compared to CD38(+/+) mice. This enhanced glomerular injury in CD38(−/−) or CD38-shRNA mice was accompanied by increased albuminuria and proteinuria. DOCA/high salt treatment further decreased the expression of epithelial markers and increased the abundance of mesenchymal markers, which were accompanied by more increased glomerular damage index and mean arterial pressure in CD38(−/−) and CD38-shRNA mice than CD38(+/+) mice. In vitro studies showed that inhibition of CD38 enhances the EMT in podocytes. In conclusion, our observations reveal that the normal expression of CD38 importantly contributes to the differentiation and function of podocytes and the defect of this gene expression may be a critical mechanism inducing EMT and consequently resulting in glomerular injury and sclerosis. Blackwell Publishing Ltd 2012-08 2012-07-29 /pmc/articles/PMC3270217/ /pubmed/21992601 http://dx.doi.org/10.1111/j.1582-4934.2011.01462.x Text en Copyright © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
spellingShingle Original Articles
Boini, Krishna M
Xia, Min
Xiong, Jing
Li, Caixia
Payne, Lori P
Li, Pin-Lan
Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title_full Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title_fullStr Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title_full_unstemmed Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title_short Implication of CD38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
title_sort implication of cd38 gene in podocyte epithelial-to-mesenchymal transition and glomerular sclerosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270217/
https://www.ncbi.nlm.nih.gov/pubmed/21992601
http://dx.doi.org/10.1111/j.1582-4934.2011.01462.x
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