シミズ　タツヤ   SHIMIZU Tatsuya   清水　達也    所属   研究施設 研究施設    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	GATA6 regulates anti-angiogenic properties in human cardiac fibroblasts via modulating LYPD1 expression
掲載誌名	正式名：Regenerative Therapy ISSNコード：2352-3204
巻・号・頁	23,pp.8-16
著者・共著者	MASUDA Shinako†, MATSUURA Katsuhisa*, SHIMIZU Tatsuya
担当区分	最終著者
発行年月	2023/06
概要	INTRODUCTION:Fibroblasts contribute to the structure and function of tissue and organs; however, their properties differ in each organ given the topographic variation in gene expression among tissues. We previously reported that LYPD1, which is expressed in cardiac fibroblasts, has the capacity to inhibit sprouting of vascular endothelial cells. LYPD1 has been shown to be highly expressed in the human brain and heart, but the regulation of LYPD1 expression in cardiac fibroblasts has not been elucidated in detail.METHODS:To identify the LYPD1-modulating transcription factor, motif enrichment analysis and differential expressed gene analysis using microarray data were performed. Quantitative real-time PCR was used to evaluate gene expression. Gene silencing were performed by transfection of siRNA. Western blot analyzed protein expression in NHCF-a. To assess the effect of GATA6 on the regulation of LYPD1 gene expression, dual-luciferase reporter assay was performed. Co-culture and rescue experiments were performed to evaluate endothelial network formation.RESULTS:Motif enrichment analysis and differential expressed gene analysis using microarray data and quantitative real-time PCR revealed that CUX1, GATA6, and MAFK were candidate transcription factors. Of these, the inhibition of GATA6 expression using siRNA decreased LYPD1 gene expression and co-expression of GATA6 with a reporter vector containing the upstream sequence of the LYPD1 gene resulted in increased reporter activity. Endothelial cell network formation was attenuated when co-cultured with cardiac fibroblasts, but it was significantly restored when co-cultured with cardiac fibroblasts wherein the expression of GATA6 was knocked down with siRNA.CONCLUSION:GATA6 regulate the anti-angiogenic properties of cardiac fibroblasts by modulating LYPD1 expression.
DOI	10.1016/j.reth.2023.02.005
PMID	37251737