MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization
ABSTRACTUrinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02094-23 |
| _version_ | 1797378875199586304 |
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| author | Changying Wang Hongyan Cheng Fenglian Yan Hui Zhang Junfeng Zhang Chunxia Li Mingsheng Zhao Dongmei Shi Huabao Xiong |
| author_facet | Changying Wang Hongyan Cheng Fenglian Yan Hui Zhang Junfeng Zhang Chunxia Li Mingsheng Zhao Dongmei Shi Huabao Xiong |
| author_sort | Changying Wang |
| collection | DOAJ |
| description | ABSTRACTUrinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b (miR-146b) deficiency aggravates kidney injury during UTIs caused by UPEC. In a mouse kidney infection model utilizing urosepsis isolate CFT073, we found that miR-146b expression significantly increased in the early stages of UPEC infection. Also, miR-146b-deficient mice displayed exacerbated inflammation in the kidney injury with severe M1 macrophage infiltration. Additionally, the results showed that miR-146b targeted interferon regulatory factor 5-regulated M1 macrophage polarization during UTIs. The results suggested that miR-146b contributed significantly to the control of kidney damage during UTIs, highlighting that miR-146b might be used as a novel therapeutic target for treating kidney injury during UTIs.IMPORTANCEKidney injury during acute urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection. |
| first_indexed | 2024-03-08T20:13:56Z |
| format | Article |
| id | doaj.art-4960f7cbd2734af5bbaf899e4c749c4f |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-03-08T20:13:56Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-4960f7cbd2734af5bbaf899e4c749c4f2023-12-22T19:53:43ZengAmerican Society for MicrobiologymBio2150-75112023-12-0114610.1128/mbio.02094-23MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarizationChangying Wang0Hongyan Cheng1Fenglian Yan2Hui Zhang3Junfeng Zhang4Chunxia Li5Mingsheng Zhao6Dongmei Shi7Huabao Xiong8Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaDepartment of Dermatology and Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, Shandong, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaABSTRACTUrinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b (miR-146b) deficiency aggravates kidney injury during UTIs caused by UPEC. In a mouse kidney infection model utilizing urosepsis isolate CFT073, we found that miR-146b expression significantly increased in the early stages of UPEC infection. Also, miR-146b-deficient mice displayed exacerbated inflammation in the kidney injury with severe M1 macrophage infiltration. Additionally, the results showed that miR-146b targeted interferon regulatory factor 5-regulated M1 macrophage polarization during UTIs. The results suggested that miR-146b contributed significantly to the control of kidney damage during UTIs, highlighting that miR-146b might be used as a novel therapeutic target for treating kidney injury during UTIs.IMPORTANCEKidney injury during acute urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection.https://journals.asm.org/doi/10.1128/mbio.02094-23acute kidney injurymacrophage differentiationurinary tract infectionsuropathogenic Escherichia coli |
| spellingShingle | Changying Wang Hongyan Cheng Fenglian Yan Hui Zhang Junfeng Zhang Chunxia Li Mingsheng Zhao Dongmei Shi Huabao Xiong MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization mBio acute kidney injury macrophage differentiation urinary tract infections uropathogenic Escherichia coli |
| title | MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| title_full | MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| title_fullStr | MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| title_full_unstemmed | MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| title_short | MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| title_sort | microrna 146b protects kidney injury during urinary tract infections by modulating macrophage polarization |
| topic | acute kidney injury macrophage differentiation urinary tract infections uropathogenic Escherichia coli |
| url | https://journals.asm.org/doi/10.1128/mbio.02094-23 |
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