title: Developmental changes in the expression and function of TRPC6 channels related the F-actin organization during differentiation in podocytes.
abstract: The transient receptor potential canonical (TRPC) 6 channel is an important ion channel located in podocytes, which plays an essential role in regulating calcium homeostasis of the cell signaling. Podocytes are specialized, terminally differentiated cells surrounding glomerular capillaries, and are the subject of keen interest because of their key roles in kidney development and disease. Here we wonder whether TRPC6 channels undergo developmental changes in the expression and function during the podocyte differentiation, and whether they contribute to the maturation of podocytes. Using morphological, immunohistochemical and electrophysiological techniques, we investigated the development of distribution and expression of TRPC6 in conditionally immortalized mouse podocyte cell line. Our results showed that the distribution of TRPC6 channels changed with the maturity of podocyte differentiation. The fluorescent intensity of TRPC6 on cell surface increased, which was accompanied by a corresponding increase in the density of current flowing through the channels. TRPC6 inhibition by TRPC6 siRNA or SKF-96365, a blocker or TRP cation channels, resulted in F-actin cytoskeleton disruption only on the developmental stage of podocytes. These results strongly support the conclusion that TPRC6 is an essential component of the slit diaphragm and is required for development of glomerulus.
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tianjin University, Tianjin 300072, China; College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.
authors.forename: Pengjuan
authors.initials: P
authors.lastname: Xu
authors.affiliation: College of Life Science, Nankai University, Tianjin 300071, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China. Electronic address: zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*; D000074287:TRPC6 Cation Channel
chemical_list: D000199:Actins; D007093:Imidazoles; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium
keywords: Differentiation; F-actin; Podocyte; TRPC6 channel