STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis
Background and objectives Acute kidney injury (AKI) is one of the most common and severe clinical syndromes of diffuse proliferative lupus nephritis (DPLN), of which poor prognosis is indicated by aggravated renal function deterioration. However, the specific therapy and mechanisms of AKI in DPLN re...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2358187 |
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| author | Jianfen Zhu Yijing Chen Yulan Chen Yinqiu Lv Tianxin Chen |
| author_facet | Jianfen Zhu Yijing Chen Yulan Chen Yinqiu Lv Tianxin Chen |
| author_sort | Jianfen Zhu |
| collection | DOAJ |
| description | Background and objectives Acute kidney injury (AKI) is one of the most common and severe clinical syndromes of diffuse proliferative lupus nephritis (DPLN), of which poor prognosis is indicated by aggravated renal function deterioration. However, the specific therapy and mechanisms of AKI in DPLN remain to be explored.Methods The correlation between AKI and clinical pathological changes in DPLN patients was analyzed. Expression of STAT3 signaling was detected in MRL/lpr mice with DPLN using immunohistochemical staining and immunoblotting. Inhibition of STAT3 activation by combination therapy was assessed in MRL/lpr mice.Results Correlation analysis revealed only the interstitial leukocytes were significantly related to AKI in endocapillary DPLN patients. MRL/lpr mice treated with vehicle, which can recapitulate renal damages of DPLN patients, showed upregulation of STAT3, pSTAT3 and caspase-1 in renal cortex. FLLL32 combined with methylprednisolone therapy significantly inhibited the STAT3 activation, improved acute kidney damage, reduced the interstitial infiltration of inflammatory cells and decreased the AKI incidence in MRL/lpr mice.Conclusion STAT3 activation may play an important role in the pathogenesis of DPLN and the development of AKI. Hence, STAT3 inhibition based on the combination of FLLL32 with methylprednisolone may represent a new strategy for treatment of DPLN with AKI. |
| format | Article |
| id | doaj-art-e6cc498c40ba445ea5e901abc36d3e02 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-e6cc498c40ba445ea5e901abc36d3e022025-01-23T04:17:48ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2358187STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritisJianfen Zhu0Yijing Chen1Yulan Chen2Yinqiu Lv3Tianxin Chen4Department of Internal Medicine Nursing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of clinical College, Wenzhou Medical University, Wenzhou, ChinaDepartment of clinical College, Wenzhou Medical University, Wenzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaBackground and objectives Acute kidney injury (AKI) is one of the most common and severe clinical syndromes of diffuse proliferative lupus nephritis (DPLN), of which poor prognosis is indicated by aggravated renal function deterioration. However, the specific therapy and mechanisms of AKI in DPLN remain to be explored.Methods The correlation between AKI and clinical pathological changes in DPLN patients was analyzed. Expression of STAT3 signaling was detected in MRL/lpr mice with DPLN using immunohistochemical staining and immunoblotting. Inhibition of STAT3 activation by combination therapy was assessed in MRL/lpr mice.Results Correlation analysis revealed only the interstitial leukocytes were significantly related to AKI in endocapillary DPLN patients. MRL/lpr mice treated with vehicle, which can recapitulate renal damages of DPLN patients, showed upregulation of STAT3, pSTAT3 and caspase-1 in renal cortex. FLLL32 combined with methylprednisolone therapy significantly inhibited the STAT3 activation, improved acute kidney damage, reduced the interstitial infiltration of inflammatory cells and decreased the AKI incidence in MRL/lpr mice.Conclusion STAT3 activation may play an important role in the pathogenesis of DPLN and the development of AKI. Hence, STAT3 inhibition based on the combination of FLLL32 with methylprednisolone may represent a new strategy for treatment of DPLN with AKI.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2358187STAT3AKIlupus nephritisrenal interstitial |
| spellingShingle | Jianfen Zhu Yijing Chen Yulan Chen Yinqiu Lv Tianxin Chen STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis Renal Failure STAT3 AKI lupus nephritis renal interstitial |
| title | STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis |
| title_full | STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis |
| title_fullStr | STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis |
| title_full_unstemmed | STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis |
| title_short | STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis |
| title_sort | stat3 inhibition ameliorates renal interstitial inflammation in mrl lpr mice with diffuse proliferative lupus nephritis |
| topic | STAT3 AKI lupus nephritis renal interstitial |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2358187 |
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