Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy
Background: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. Methods...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | Spanish |
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Elsevier
2024-03-01
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| Series: | Nefrología |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0211699523001388 |
| _version_ | 1827329807444082688 |
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| author | Huilin Li Shuang Liu Dan Zhang Xue Zong Gengru Jiang Chun Zhu |
| author_facet | Huilin Li Shuang Liu Dan Zhang Xue Zong Gengru Jiang Chun Zhu |
| author_sort | Huilin Li |
| collection | DOAJ |
| description | Background: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. Methods: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. Results: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. Conclusion: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp. Resumen: Antecedentes: Los agentes de contraste pueden inducir isquemia tubular renal y daño hipóxico de manera directa o indirecta. Dado que el cloruro de cobalto (CoCl2) puede proteger los túbulos renales, el efecto protector y el mecanismo de acción potencial de CoCl2 en la nefropatía inducida por contraste (NIC) merecen ser investigados. Métodos: Se estableció un modelo de NIC en ratones para determinar el efecto protector de CoCl2 en la nefropatía in vivo. Seguidamente, se realizó un análisis proteómico por TMT para determinar las proteínas diferencialmente expresadas (DEP) y, a continuación, un análisis de enriquecimiento de ontología genética y vía KEGG. In vitro, se construyó un modelo NIC en células epiteliales de túbulos renales (HK-2) para determinar el efecto de CoCl2 en los objetivos potenciales y el rol de la proteína clave identificada en los experimentos in vivo. Resultados: El tratamiento con CoCl2 redujo los niveles de BUN y de creatinina sérica e incrementó, a la vez, los de urea y creatinina en la orina de los ratones, tras la lesión NIC. El daño a los túbulos renales en el grupo de tratamiento con CoCl2 fue significativamente menor que en el grupo de modelo NIC. Identificamos 79 DEP tras el tratamiento en el modelo in vivo con CoCl2 y observamos con frecuencia ontología genética relacionada con ferroptosis y términos de vías KEGG. De ellos, se seleccionó la haptoglobina (Hp) y se encontró que tenía un fuerte efecto renoprotector, aun cuando su nivel de expresión en el tejido renal se redujo tras el tratamiento con CoCl2. En las células HK-2, la sobreexpresión de Hp redujo la ferroptosis causada por erastina, a pesar de que el descenso de Hp negó el efecto atenuador de CoCl2 en la ferroptosis de las células HK-2. Conclusión: El CoCl2 atenuó el daño renal en el modelo NIC y se asoció este efecto al descenso de ferroptosis mediada por Hp. |
| first_indexed | 2024-03-07T15:47:31Z |
| format | Article |
| id | doaj.art-738b64e734244a63adaf5ab565f7c736 |
| institution | Directory Open Access Journal |
| issn | 0211-6995 |
| language | Spanish |
| last_indexed | 2024-03-07T15:47:31Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Nefrología |
| spelling | doaj.art-738b64e734244a63adaf5ab565f7c7362024-03-05T04:29:30ZspaElsevierNefrología0211-69952024-03-01442180193Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathyHuilin Li0Shuang Liu1Dan Zhang2Xue Zong3Gengru Jiang4Chun Zhu5Division of Nephrology, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author.Division of Nephrology, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDivision of Nephrology, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDivision of Nephrology, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDivision of Nephrology, Department of Internal Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Nephrology, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming Branch, Shanghai 202150, China; Co-corresponding author.Background: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. Methods: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. Results: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. Conclusion: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp. Resumen: Antecedentes: Los agentes de contraste pueden inducir isquemia tubular renal y daño hipóxico de manera directa o indirecta. Dado que el cloruro de cobalto (CoCl2) puede proteger los túbulos renales, el efecto protector y el mecanismo de acción potencial de CoCl2 en la nefropatía inducida por contraste (NIC) merecen ser investigados. Métodos: Se estableció un modelo de NIC en ratones para determinar el efecto protector de CoCl2 en la nefropatía in vivo. Seguidamente, se realizó un análisis proteómico por TMT para determinar las proteínas diferencialmente expresadas (DEP) y, a continuación, un análisis de enriquecimiento de ontología genética y vía KEGG. In vitro, se construyó un modelo NIC en células epiteliales de túbulos renales (HK-2) para determinar el efecto de CoCl2 en los objetivos potenciales y el rol de la proteína clave identificada en los experimentos in vivo. Resultados: El tratamiento con CoCl2 redujo los niveles de BUN y de creatinina sérica e incrementó, a la vez, los de urea y creatinina en la orina de los ratones, tras la lesión NIC. El daño a los túbulos renales en el grupo de tratamiento con CoCl2 fue significativamente menor que en el grupo de modelo NIC. Identificamos 79 DEP tras el tratamiento en el modelo in vivo con CoCl2 y observamos con frecuencia ontología genética relacionada con ferroptosis y términos de vías KEGG. De ellos, se seleccionó la haptoglobina (Hp) y se encontró que tenía un fuerte efecto renoprotector, aun cuando su nivel de expresión en el tejido renal se redujo tras el tratamiento con CoCl2. En las células HK-2, la sobreexpresión de Hp redujo la ferroptosis causada por erastina, a pesar de que el descenso de Hp negó el efecto atenuador de CoCl2 en la ferroptosis de las células HK-2. Conclusión: El CoCl2 atenuó el daño renal en el modelo NIC y se asoció este efecto al descenso de ferroptosis mediada por Hp.http://www.sciencedirect.com/science/article/pii/S0211699523001388Nefropatía inducida por contrasteCoCl2TMTCélula HK-2HpFerroptosis |
| spellingShingle | Huilin Li Shuang Liu Dan Zhang Xue Zong Gengru Jiang Chun Zhu Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy Nefrología Nefropatía inducida por contraste CoCl2 TMT Célula HK-2 Hp Ferroptosis |
| title | Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy |
| title_full | Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy |
| title_fullStr | Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy |
| title_full_unstemmed | Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy |
| title_short | Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy |
| title_sort | dysregulation of ferroptosis may participate in the mitigating effect of cocl2 on contrast induced nephropathy |
| topic | Nefropatía inducida por contraste CoCl2 TMT Célula HK-2 Hp Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0211699523001388 |
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