Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats
Chronic kidney disease (CKD) is a common outcome of many kidney diseases. Interstitial fibrosis and tubular atrophy (IFTA) is a histologic hallmark of CKD. Hematuria is a common symptom in many human kidney diseases. Free hemoglobin may affect tubular epithelial cells by generating reactive oxygen s...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1036599b508244d49fa433a0f92a955c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1036599b508244d49fa433a0f92a955c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1036599b508244d49fa433a0f92a955c2021-12-01T00:03:13ZChronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats2296-858X10.3389/fmed.2021.753506https://doaj.org/article/1036599b508244d49fa433a0f92a955c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.753506/fullhttps://doaj.org/toc/2296-858XChronic kidney disease (CKD) is a common outcome of many kidney diseases. Interstitial fibrosis and tubular atrophy (IFTA) is a histologic hallmark of CKD. Hematuria is a common symptom in many human kidney diseases. Free hemoglobin may affect tubular epithelial cells by generating reactive oxygen species (ROS). Epithelial–mesenchymal transition (EMT) of the tubular epithelial cells has been shown to play an important role in the IFTA development. The aim of this study was to determine the effects of chronic hematuria on the CKD progression in 5/6 nephrectomy (5/6NE) rat model of CKD. 5/6 NE rats were treated with oral warfarin (0.5 mg/kg/day) or vehicle (control). The animals were monitored for 26 weeks, while prothrombin time (PT), serum creatinine (SCr), and hematuria were measured weekly. Staining for iron, trichrome, and EMT (vimentin, E-cadherin, smooth muscle actin) markers was performed on the remnant kidneys. ROS were detected in the kidneys by protein carbonyl assay and immunohistochemistry for heme oxygenase 1 (HMOX1), at the end of the study. Apoptosis was detected by TUNEL assay. Warfarin treatment resulted in a PT increase 1.5–2.5 times from control and an increase in hematuria and SCr. Histologically, warfarin-treated animals had more iron-positive tubular epithelial cells and increased IFTA as compared to control (42.9 ± 17% vs. 18.3 ± 2.6%). ROS were increased in the kidney in warfarin-treated rats. The number of tubules that show evidence of EMT was significantly higher in warfarin-treated 5/6NE as compared to control 5/6NE rats. The number of apoptotic tubular epithelial cells was higher in warfarin-treated 5/6 NE rats. Chronic hematuria results in increased iron-positive tubular epithelial cells, EMT, apoptosis, and more prominent IFTA in CKD rats. Our data suggest an important role of chronic hematuria in the progression of CKD.Min XiaoAjay K. MedipallyLaura BiedermanLaura BiedermanAnjali A. SatoskarIouri IvanovBrad H. RovinSergey V. BrodskyFrontiers Media S.A.articlehematuriachronic kidney diseaseanticoagulationepithelial mesenchymal transition (EMT)ironMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
hematuria chronic kidney disease anticoagulation epithelial mesenchymal transition (EMT) iron Medicine (General) R5-920 |
| spellingShingle |
hematuria chronic kidney disease anticoagulation epithelial mesenchymal transition (EMT) iron Medicine (General) R5-920 Min Xiao Ajay K. Medipally Laura Biederman Laura Biederman Anjali A. Satoskar Iouri Ivanov Brad H. Rovin Sergey V. Brodsky Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| description |
Chronic kidney disease (CKD) is a common outcome of many kidney diseases. Interstitial fibrosis and tubular atrophy (IFTA) is a histologic hallmark of CKD. Hematuria is a common symptom in many human kidney diseases. Free hemoglobin may affect tubular epithelial cells by generating reactive oxygen species (ROS). Epithelial–mesenchymal transition (EMT) of the tubular epithelial cells has been shown to play an important role in the IFTA development. The aim of this study was to determine the effects of chronic hematuria on the CKD progression in 5/6 nephrectomy (5/6NE) rat model of CKD. 5/6 NE rats were treated with oral warfarin (0.5 mg/kg/day) or vehicle (control). The animals were monitored for 26 weeks, while prothrombin time (PT), serum creatinine (SCr), and hematuria were measured weekly. Staining for iron, trichrome, and EMT (vimentin, E-cadherin, smooth muscle actin) markers was performed on the remnant kidneys. ROS were detected in the kidneys by protein carbonyl assay and immunohistochemistry for heme oxygenase 1 (HMOX1), at the end of the study. Apoptosis was detected by TUNEL assay. Warfarin treatment resulted in a PT increase 1.5–2.5 times from control and an increase in hematuria and SCr. Histologically, warfarin-treated animals had more iron-positive tubular epithelial cells and increased IFTA as compared to control (42.9 ± 17% vs. 18.3 ± 2.6%). ROS were increased in the kidney in warfarin-treated rats. The number of tubules that show evidence of EMT was significantly higher in warfarin-treated 5/6NE as compared to control 5/6NE rats. The number of apoptotic tubular epithelial cells was higher in warfarin-treated 5/6 NE rats. Chronic hematuria results in increased iron-positive tubular epithelial cells, EMT, apoptosis, and more prominent IFTA in CKD rats. Our data suggest an important role of chronic hematuria in the progression of CKD. |
| format |
article |
| author |
Min Xiao Ajay K. Medipally Laura Biederman Laura Biederman Anjali A. Satoskar Iouri Ivanov Brad H. Rovin Sergey V. Brodsky |
| author_facet |
Min Xiao Ajay K. Medipally Laura Biederman Laura Biederman Anjali A. Satoskar Iouri Ivanov Brad H. Rovin Sergey V. Brodsky |
| author_sort |
Min Xiao |
| title |
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| title_short |
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| title_full |
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| title_fullStr |
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| title_full_unstemmed |
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats |
| title_sort |
chronic hematuria increases chronic kidney injury and epithelial–mesenchymal transition in 5/6 nephrectomy rats |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/1036599b508244d49fa433a0f92a955c |
| work_keys_str_mv |
AT minxiao chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT ajaykmedipally chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT laurabiederman chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT laurabiederman chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT anjaliasatoskar chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT iouriivanov chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT bradhrovin chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats AT sergeyvbrodsky chronichematuriaincreaseschronickidneyinjuryandepithelialmesenchymaltransitionin56nephrectomyrats |
| _version_ |
1718406124753911808 |