FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin

Introduction Familial focal and segmental glomerulosclerosis (FFSGS) was found in a large cohort of patients in our previous study. Under the sponsorship of the National Natural Science Foundation of China, we conducted linkage analysis and full exon sequencing on the genomes of 54 patients diagnose...

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Autores principales:	Zhou Chen, Yinghui Zhang, Xuezhi Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Termedia Publishing House 2018
Materias:	cytoskeleton fam40a mouse podocyte f-actin nephrin Medicine R
Acceso en línea:	https://doaj.org/article/c919912702d0427cae879bb24d8d0f41
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spelling	oai:doaj.org-article:c919912702d0427cae879bb24d8d0f412021-12-02T18:33:21ZFAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin1734-19221896-915110.5114/aoms.2018.73138https://doaj.org/article/c919912702d0427cae879bb24d8d0f412018-12-01T00:00:00Zhttps://www.archivesofmedicalscience.com/FAM40A-alters-the-cytoskeleton-of-podocytes-in-familial-focal-and-segmental-glomerulosclerosis,80899,0,2.htmlhttps://doaj.org/toc/1734-1922https://doaj.org/toc/1896-9151Introduction Familial focal and segmental glomerulosclerosis (FFSGS) was found in a large cohort of patients in our previous study. Under the sponsorship of the National Natural Science Foundation of China, we conducted linkage analysis and full exon sequencing on the genomes of 54 patients diagnosed with FFSGS. The results revealed a FAM40A gene signature in those patients. To determine whether FAM40A was associated with podocyte lesions and whether changes in the podocyte cytoskeleton could affect podocyte function, mouse podocytes (MPs) were used in this study. Material and methods FAM40A silencing, over-expression and mutant-type over-expression models of renal MPs were established, whereby roles of wild-type FAM40A and mutant FAM40A (c.1562T>C, p521M>T) in regulating the function of the MP cytoskeleton were explored by using cellular immunofluorescence, RT-qPCR and Western blot. Results FAM40A was expressed and localized in MPs and significantly enriched in the nucleus and perinuclear zone. Changes of FAM40A expression altered the morphology of the MPs and their cytoskeletal organization, which was characterized by disordered distribution of F-actin, loss of the foot process architecture and the functional protein of the slit diaphragm nephrin (p < 0.05 or p T) led to the formation of round and blunt morphology of the MPs and loss of the foot-process structure. In addition, expression of the cytoskeletal protein F-actin was increased and concentrated in FAM40A mutated cells, whereas the expression of nephrin decreased in those cells (p T) was able to alter the morphology and cytoskeleton of the MPs, and to decrease the expression of nephrin, which may be the main factor contributing to FSGS.Zhou ChenYinghui ZhangXuezhi ZhaoTermedia Publishing Housearticlecytoskeletonfam40amouse podocytef-actinnephrinMedicineRENArchives of Medical Science, Vol 15, Iss 1, Pp 165-173 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytoskeleton fam40a mouse podocyte f-actin nephrin Medicine R
spellingShingle	cytoskeleton fam40a mouse podocyte f-actin nephrin Medicine R Zhou Chen Yinghui Zhang Xuezhi Zhao FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
description	Introduction Familial focal and segmental glomerulosclerosis (FFSGS) was found in a large cohort of patients in our previous study. Under the sponsorship of the National Natural Science Foundation of China, we conducted linkage analysis and full exon sequencing on the genomes of 54 patients diagnosed with FFSGS. The results revealed a FAM40A gene signature in those patients. To determine whether FAM40A was associated with podocyte lesions and whether changes in the podocyte cytoskeleton could affect podocyte function, mouse podocytes (MPs) were used in this study. Material and methods FAM40A silencing, over-expression and mutant-type over-expression models of renal MPs were established, whereby roles of wild-type FAM40A and mutant FAM40A (c.1562T>C, p521M>T) in regulating the function of the MP cytoskeleton were explored by using cellular immunofluorescence, RT-qPCR and Western blot. Results FAM40A was expressed and localized in MPs and significantly enriched in the nucleus and perinuclear zone. Changes of FAM40A expression altered the morphology of the MPs and their cytoskeletal organization, which was characterized by disordered distribution of F-actin, loss of the foot process architecture and the functional protein of the slit diaphragm nephrin (p < 0.05 or p T) led to the formation of round and blunt morphology of the MPs and loss of the foot-process structure. In addition, expression of the cytoskeletal protein F-actin was increased and concentrated in FAM40A mutated cells, whereas the expression of nephrin decreased in those cells (p T) was able to alter the morphology and cytoskeleton of the MPs, and to decrease the expression of nephrin, which may be the main factor contributing to FSGS.
format	article
author	Zhou Chen Yinghui Zhang Xuezhi Zhao
author_facet	Zhou Chen Yinghui Zhang Xuezhi Zhao
author_sort	Zhou Chen
title	FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
title_short	FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
title_full	FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
title_fullStr	FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
title_full_unstemmed	FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin
title_sort	fam40a alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating f-actin and nephrin
publisher	Termedia Publishing House
publishDate	2018
url	https://doaj.org/article/c919912702d0427cae879bb24d8d0f41
work_keys_str_mv	AT zhouchen fam40aaltersthecytoskeletonofpodocytesinfamilialfocalandsegmentalglomerulosclerosisbyregulatingfactinandnephrin AT yinghuizhang fam40aaltersthecytoskeletonofpodocytesinfamilialfocalandsegmentalglomerulosclerosisbyregulatingfactinandnephrin AT xuezhizhao fam40aaltersthecytoskeletonofpodocytesinfamilialfocalandsegmentalglomerulosclerosisbyregulatingfactinandnephrin
_version_	1718377944865308672

FAM40A alters the cytoskeleton of podocytes in familial focal and segmental glomerulosclerosis by regulating F-actin and nephrin

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