L Luo1, G Luo2, Q Fang3, Z Sun4. 1. Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China. 2. Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China. 3. Department of Nursing, Guizhou Province People's Hospital, Guiyang, China. 4. Department of Urology Surgery, Guizhou Province People's Hospital, Guiyang, China. Electronic address: szl7710@hotmail.com.
Abstract
BACKGROUND: Late kidney allograft dysfunction is becoming a significant problem and tubular atrophy and interstitial fibrosis are main causes. It was reported that hypoxia could induce epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells (TECs), and hypoxia-inducible factor-1 (HIF-1) is one of the important regulators of cellular adaptive to hypoxia. METHODS: In this study, we used an HIF-1αΔODD-expressing adenovirus, which could stably and functionally express HIF-1α under normoxia conditions, and used a hypoxia/reoxygenation cell model to simulate ischemia/reperfusion (I/R) injury in vitro, to investigate the effect of HIF-1α on EMT-related gene expressions. RESULTS: Our results demonstrated that HIF-1α could significantly upregulate α-smooth muscle actin expression, and reduced the E-cadherin expression in HK-2 cells during I/R injury. Moreover, miR-21 expression had a positive correlation with HIF-1α in this process. CONCLUSION: These results suggest that HIF-1α may promote the EMT development through regulating fibrotic gene expression during I/R injury in human renal TECs, and miR-21 could be among the important regulatory pathways in the process.
BACKGROUND: Late kidney allograft dysfunction is becoming a significant problem and tubular atrophy and interstitial fibrosis are main causes. It was reported that hypoxia could induce epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells (TECs), and hypoxia-inducible factor-1 (HIF-1) is one of the important regulators of cellular adaptive to hypoxia. METHODS: In this study, we used an HIF-1αΔODD-expressing adenovirus, which could stably and functionally express HIF-1α under normoxia conditions, and used a hypoxia/reoxygenation cell model to simulate ischemia/reperfusion (I/R) injury in vitro, to investigate the effect of HIF-1α on EMT-related gene expressions. RESULTS: Our results demonstrated that HIF-1α could significantly upregulate α-smooth muscle actin expression, and reduced the E-cadherin expression in HK-2 cells during I/R injury. Moreover, miR-21 expression had a positive correlation with HIF-1α in this process. CONCLUSION: These results suggest that HIF-1α may promote the EMT development through regulating fibrotic gene expression during I/R injury in human renal TECs, and miR-21 could be among the important regulatory pathways in the process.
Authors: Elisa Conde; Sara Giménez-Moyano; Laura Martín-Gómez; Macarena Rodríguez; M Edurne Ramos; Elia Aguado-Fraile; Ignacio Blanco-Sanchez; Ana Saiz; María Laura García-Bermejo Journal: Sci Rep Date: 2017-01-20 Impact factor: 4.379