CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition

Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus. Accumulating studies suggest that the deregulation of circular RNA (circRNA) is involved in DN pathogenesis. This study aimed to investigate the role of circSMAD4 in DN models. Methods Mice were treated with...

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Autores principales:	Rina Wu, Zheli Niu, Guangwei Ren, Lin Ruan, Lijun Sun
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	circSMAD4 miR-377-3p BMP7 Diabetic nephropathy Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/b3624a0af4b343d1903fe09b77c6607b
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spelling	oai:doaj.org-article:b3624a0af4b343d1903fe09b77c6607b2021-11-21T12:40:13ZCircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition10.1186/s13098-021-00753-11758-5996https://doaj.org/article/b3624a0af4b343d1903fe09b77c6607b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13098-021-00753-1https://doaj.org/toc/1758-5996Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus. Accumulating studies suggest that the deregulation of circular RNA (circRNA) is involved in DN pathogenesis. This study aimed to investigate the role of circSMAD4 in DN models. Methods Mice were treated with streptozotocin to establish DN models in vivo. Mouse glomerulus mesangial cells (SV40-MES13) were treated with high glucose to establish DN models in vitro. The expression of circSMAD4, miR-377-3p and bone morphogenetic protein 7 (BMP7) mRNA was measured by quantitative real-time PCR (qPCR). The releases of inflammatory factors were examined by ELISA. The protein levels of fibrosis-related markers, apoptosis-related markers and BMP7 were checked by western blot. Cell apoptosis was monitored by flow cytometry assay. The predicted relationship between miR-377-3p and circSMAD4 or BMP7 was validated by dual-luciferase reporter assay or pull-down assay. Results CircSMAD4 was poorly expressed in DN mice and HG-treated SV40-MES13 cells. HG induced SV40-MES13 cell inflammation, extracellular matrix (ECM) deposition and apoptosis. CircSMAD4 overexpression alleviated, while circSMAD4 knockdown aggravated HG-induced SV40-MES13 cell injuries. MiR-377-3p was targeted by circSMAD4, and miR-377-3p enrichment partly reversed the effects of circSMAD4 overexpression. BMP7 was a target of miR-377-3p, and circSMAD4 regulated BMP7 expression by targeting miR-377-3p. MiR-377-3p overexpression aggravated HG-induced injuries by suppressing BMP7. Conclusion CircSMAD4 alleviates HG-induced SV40-MES13 cell inflammation, ECM deposition and apoptosis by relieving miR-377-3p-mediated inhibition on BMP7 in DN progression.Rina WuZheli NiuGuangwei RenLin RuanLijun SunBMCarticlecircSMAD4miR-377-3pBMP7Diabetic nephropathyNutritional diseases. Deficiency diseasesRC620-627ENDiabetology & Metabolic Syndrome, Vol 13, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circSMAD4 miR-377-3p BMP7 Diabetic nephropathy Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	circSMAD4 miR-377-3p BMP7 Diabetic nephropathy Nutritional diseases. Deficiency diseases RC620-627 Rina Wu Zheli Niu Guangwei Ren Lin Ruan Lijun Sun CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
description	Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus. Accumulating studies suggest that the deregulation of circular RNA (circRNA) is involved in DN pathogenesis. This study aimed to investigate the role of circSMAD4 in DN models. Methods Mice were treated with streptozotocin to establish DN models in vivo. Mouse glomerulus mesangial cells (SV40-MES13) were treated with high glucose to establish DN models in vitro. The expression of circSMAD4, miR-377-3p and bone morphogenetic protein 7 (BMP7) mRNA was measured by quantitative real-time PCR (qPCR). The releases of inflammatory factors were examined by ELISA. The protein levels of fibrosis-related markers, apoptosis-related markers and BMP7 were checked by western blot. Cell apoptosis was monitored by flow cytometry assay. The predicted relationship between miR-377-3p and circSMAD4 or BMP7 was validated by dual-luciferase reporter assay or pull-down assay. Results CircSMAD4 was poorly expressed in DN mice and HG-treated SV40-MES13 cells. HG induced SV40-MES13 cell inflammation, extracellular matrix (ECM) deposition and apoptosis. CircSMAD4 overexpression alleviated, while circSMAD4 knockdown aggravated HG-induced SV40-MES13 cell injuries. MiR-377-3p was targeted by circSMAD4, and miR-377-3p enrichment partly reversed the effects of circSMAD4 overexpression. BMP7 was a target of miR-377-3p, and circSMAD4 regulated BMP7 expression by targeting miR-377-3p. MiR-377-3p overexpression aggravated HG-induced injuries by suppressing BMP7. Conclusion CircSMAD4 alleviates HG-induced SV40-MES13 cell inflammation, ECM deposition and apoptosis by relieving miR-377-3p-mediated inhibition on BMP7 in DN progression.
format	article
author	Rina Wu Zheli Niu Guangwei Ren Lin Ruan Lijun Sun
author_facet	Rina Wu Zheli Niu Guangwei Ren Lin Ruan Lijun Sun
author_sort	Rina Wu
title	CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
title_short	CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
title_full	CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
title_fullStr	CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
title_full_unstemmed	CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
title_sort	circsmad4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving mir-377-3p-mediated bmp7 inhibition
publisher	BMC
publishDate	2021
url	https://doaj.org/article/b3624a0af4b343d1903fe09b77c6607b
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CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition

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