MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis
Introduction and objectives: Acute kidney injury (AKI) is a common devastating complication characterized by an abrupt loss of renal function. It is of great significance to explore promising biomarkers for AKI treatment. Materials and methods: Here, we established LPS (lipopolysaccharide)-induced A...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | Spanish |
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Elsevier
2023-12-01
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| Series: | Nefrología |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0211699523000103 |
| _version_ | 1797390567585349632 |
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| author | Xiaobing Ji Xiaodong Liu Xiangxiang Li Xin Du Li Fan |
| author_facet | Xiaobing Ji Xiaodong Liu Xiangxiang Li Xin Du Li Fan |
| author_sort | Xiaobing Ji |
| collection | DOAJ |
| description | Introduction and objectives: Acute kidney injury (AKI) is a common devastating complication characterized by an abrupt loss of renal function. It is of great significance to explore promising biomarkers for AKI treatment. Materials and methods: Here, we established LPS (lipopolysaccharide)-induced AKI mice models and LPS-induced AKI mouse renal tubular epithelial cell model. The severity of AKI was determined by the levels of BUN (blood urea nitrogen) and SCr (serum creatinine), the observation of pathological section as well as the renal tubular injury score. The apoptosis was determined by the measurement of Caspase-3 and Caspase-9 activities, and cell apoptosis assays. qRT-PCR (quantitative real-time PCR) and western blot revealed that miR-322-5p (microRNA-322-5p) was up-regulated in LPS -induced AKI models while Tbx21 (T-box transcription factor 21) was down-regulated in LPS-induced AKI models. Dual-luciferase reporter and RNA pulldown assays detected the interaction of Tbx21 with miR-322-5p. Results: We found that miR-322-5p was overtly over-expressed in the in vitro LPS-induced AKI model and promoted the apoptosis of AKI mouse renal tubular epithelial cells via inhibiting Tbx21, which suppressed the mitochondrial fission and cell apoptosis through MAPK/ERK (mitogen-activated protein kinase/extracellular signal-related kinase) pathway. Conclusions: We demonstrated that miR-322-5p promotes LPS-induced mouse AKI by regulating Tbx21/MAPK/ERK axis, which might provide new sights for AKI research. Resumen: Introducción y objetivos: La insuficiencia renal aguda (IRA) es una complicación común devastadora caracterizada por una pérdida abrupta de la función renal. Es de vital importancia explorar biomarcadores prometedores para el tratamiento de la IRA. Materiales y métodos: Establecimos aquí un modelo de ratones con IRA inducido por lipopolisacáridos (LPS) y un modelo de células epiteliales del túbulo renal en ratones. La severidad de IRA fue determinada por los niveles de NUS (nitrógeno ureico en sangre) y SCr (creatinina sérica), la observación de la sección patológica, así como la puntuación del daño renal tubular. La apoptosis fue determinada mediante la medición de las actividades de Caspasa-3 y Caspasa-9, y los ensayos de apoptosis celular. Las pruebas qRT-PCR (PCR cuantitativa en tiempo real) y Western blot revelaron que miR-322-5p (microRNA-322-5p) se incrementaba en los modelos de IRA inducidos por LPS, mientras que Tbx21 (factor 21 de transcripción de T-box) disminuía en los modelos de IRA inducidos por LPS. Los ensayos del reportador de luciferasa dual y de precipitación pulldown de ARN detectaron la interacción entre Tbx21 y miR-322-5p. Resultados: Encontramos que miR-322-5p se hallaba manifiestamente incrementado en el modelo in vitro de IRA inducido por LPS, y promovió la apoptosis de células epiteliales del túbulo renal de IRA en ratones mediante la inhibición de Tbx21, lo cual suprimió la fisión mitocondrial y la apoptosis a través de la vía MAPK/ERK (proteína quinasa activada por mitógeno/quinasa relacionada con la señal extracelular). Conclusiones: Demostramos que miR-322-5p promueve la IRA inducida por LPS en ratones mediante la regulación del eje Tbx21/MAPK/ERK, lo cual podría aportar una percepción nueva para la investigación sobre la IRA. |
| first_indexed | 2024-03-08T23:13:43Z |
| format | Article |
| id | doaj.art-b07744df49834822927a13181f544dd5 |
| institution | Directory Open Access Journal |
| issn | 0211-6995 |
| language | Spanish |
| last_indexed | 2024-03-08T23:13:43Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Nefrología |
| spelling | doaj.art-b07744df49834822927a13181f544dd52023-12-15T07:22:35ZspaElsevierNefrología0211-69952023-12-0143820MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axisXiaobing Ji0Xiaodong Liu1Xiangxiang Li2Xin Du3Li Fan4Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, ChinaDepartment of Nephrology, The Second People's Hospital of Lianyungang,Affiliated to Kangda College of Nanjing Medical University, Lianyungang 222023, Jiangsu, ChinaDepartment of Nephrology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing 210039, Jiangsu, ChinaDepartment of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, ChinaDepartment of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China; Corresponding author.Introduction and objectives: Acute kidney injury (AKI) is a common devastating complication characterized by an abrupt loss of renal function. It is of great significance to explore promising biomarkers for AKI treatment. Materials and methods: Here, we established LPS (lipopolysaccharide)-induced AKI mice models and LPS-induced AKI mouse renal tubular epithelial cell model. The severity of AKI was determined by the levels of BUN (blood urea nitrogen) and SCr (serum creatinine), the observation of pathological section as well as the renal tubular injury score. The apoptosis was determined by the measurement of Caspase-3 and Caspase-9 activities, and cell apoptosis assays. qRT-PCR (quantitative real-time PCR) and western blot revealed that miR-322-5p (microRNA-322-5p) was up-regulated in LPS -induced AKI models while Tbx21 (T-box transcription factor 21) was down-regulated in LPS-induced AKI models. Dual-luciferase reporter and RNA pulldown assays detected the interaction of Tbx21 with miR-322-5p. Results: We found that miR-322-5p was overtly over-expressed in the in vitro LPS-induced AKI model and promoted the apoptosis of AKI mouse renal tubular epithelial cells via inhibiting Tbx21, which suppressed the mitochondrial fission and cell apoptosis through MAPK/ERK (mitogen-activated protein kinase/extracellular signal-related kinase) pathway. Conclusions: We demonstrated that miR-322-5p promotes LPS-induced mouse AKI by regulating Tbx21/MAPK/ERK axis, which might provide new sights for AKI research. Resumen: Introducción y objetivos: La insuficiencia renal aguda (IRA) es una complicación común devastadora caracterizada por una pérdida abrupta de la función renal. Es de vital importancia explorar biomarcadores prometedores para el tratamiento de la IRA. Materiales y métodos: Establecimos aquí un modelo de ratones con IRA inducido por lipopolisacáridos (LPS) y un modelo de células epiteliales del túbulo renal en ratones. La severidad de IRA fue determinada por los niveles de NUS (nitrógeno ureico en sangre) y SCr (creatinina sérica), la observación de la sección patológica, así como la puntuación del daño renal tubular. La apoptosis fue determinada mediante la medición de las actividades de Caspasa-3 y Caspasa-9, y los ensayos de apoptosis celular. Las pruebas qRT-PCR (PCR cuantitativa en tiempo real) y Western blot revelaron que miR-322-5p (microRNA-322-5p) se incrementaba en los modelos de IRA inducidos por LPS, mientras que Tbx21 (factor 21 de transcripción de T-box) disminuía en los modelos de IRA inducidos por LPS. Los ensayos del reportador de luciferasa dual y de precipitación pulldown de ARN detectaron la interacción entre Tbx21 y miR-322-5p. Resultados: Encontramos que miR-322-5p se hallaba manifiestamente incrementado en el modelo in vitro de IRA inducido por LPS, y promovió la apoptosis de células epiteliales del túbulo renal de IRA en ratones mediante la inhibición de Tbx21, lo cual suprimió la fisión mitocondrial y la apoptosis a través de la vía MAPK/ERK (proteína quinasa activada por mitógeno/quinasa relacionada con la señal extracelular). Conclusiones: Demostramos que miR-322-5p promueve la IRA inducida por LPS en ratones mediante la regulación del eje Tbx21/MAPK/ERK, lo cual podría aportar una percepción nueva para la investigación sobre la IRA.http://www.sciencedirect.com/science/article/pii/S0211699523000103miR-322-5pInsuficiencia renal agudaTbx21Vía de señalización de MAPK/ERK |
| spellingShingle | Xiaobing Ji Xiaodong Liu Xiangxiang Li Xin Du Li Fan MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis Nefrología miR-322-5p Insuficiencia renal aguda Tbx21 Vía de señalización de MAPK/ERK |
| title | MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis |
| title_full | MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis |
| title_fullStr | MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis |
| title_full_unstemmed | MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis |
| title_short | MicroRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis |
| title_sort | microrna 322 5p promotes lipopolysaccharide induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating t box transcription factor 21 mitogen activated protein kinase extracellular signal related kinase axis |
| topic | miR-322-5p Insuficiencia renal aguda Tbx21 Vía de señalización de MAPK/ERK |
| url | http://www.sciencedirect.com/science/article/pii/S0211699523000103 |
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