Anwaier Apizi, Jian Li, Yan Li, Zhaoxia Yu, Ruifeng Chai
{"title":"抑制miRNA-939表达减轻脓毒症大鼠肺肾损害的机制","authors":"Anwaier Apizi, Jian Li, Yan Li, Zhaoxia Yu, Ruifeng Chai","doi":"10.5603/fhc.101988","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis, a life-threatening condition caused by a host response that goes out of control, leads to severe organ dysfunction. MicroRNA 939 (miRNA-939) plays a pivotal role in this process by post-transcriptionally regulating the mRNA expression of key enzymes in the NO/cGMP pathway. This pathway is crucial in the development of refractory hypotension and organ failure in sepsis. The aim of the study was to explore the effects of miRNA-939 on a caecum ligation puncture (CLP) rat model of sepsis in kidneys and lungs in order to elucidate its role in modulating the NO/cGMP pathway and related organ protection mechanisms.</p><p><strong>Material and methods: </strong>To explore the effects of miRNA-939 on sepsis, we established three groups of rats: a sham surgery group, a sepsis model group, and an intervention group treated with LNA-antimiR targeting miRNA-939, which was administered via tail vein injection (the locked nucleic acid (LNA) group). We assessed miRNA-939 levels in serum, kidneys and lungs using a reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase (sGC) were quantified using Western blotting. Serum nitric oxide (NO) levels were determined using the nitrate reductase method.</p><p><strong>Results: </strong>Compared to the sham group, the rats in the sepsis model group exhibited significantly elevated levels of miRNA-939 in serum, with distinct peaks at 12, 24, and 36 h post-sepsis induction. Similarly, the protein levels of iNOS and sGC (sGCα1 and sGCβ1 subunits) in kidneys and lungs were markedly higher in the sepsis group. Serum NO levels were also significantly elevated in the sepsis group compared to the sham group. Importantly, inhibition of miRNA-939 in the LNA group led to a significant reduction in the tissue levels of iNOS, sGCα1, sGCβ1, and serum NO within the NO/cGMP pathway, alongside mitigating inflammatory damage to kidneys and lungs.</p><p><strong>Conclusions: </strong>Inhibiting miRNA-939 significantly reduces the expression of iNOS, sGCα1, sGCβ1, and NO in the NO/cGMP pathway in CLP-exposed rats, thereby alleviating inflammatory organ damage in sepsis. These findings highlight the therapeutic potential of targeting miRNA-939 in the management of sepsis-induced organ dysfunction.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanisms of alleviating sepsis-induced rat lung and kidney damage by inhibiting expression of miRNA-939.\",\"authors\":\"Anwaier Apizi, Jian Li, Yan Li, Zhaoxia Yu, Ruifeng Chai\",\"doi\":\"10.5603/fhc.101988\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Sepsis, a life-threatening condition caused by a host response that goes out of control, leads to severe organ dysfunction. MicroRNA 939 (miRNA-939) plays a pivotal role in this process by post-transcriptionally regulating the mRNA expression of key enzymes in the NO/cGMP pathway. This pathway is crucial in the development of refractory hypotension and organ failure in sepsis. The aim of the study was to explore the effects of miRNA-939 on a caecum ligation puncture (CLP) rat model of sepsis in kidneys and lungs in order to elucidate its role in modulating the NO/cGMP pathway and related organ protection mechanisms.</p><p><strong>Material and methods: </strong>To explore the effects of miRNA-939 on sepsis, we established three groups of rats: a sham surgery group, a sepsis model group, and an intervention group treated with LNA-antimiR targeting miRNA-939, which was administered via tail vein injection (the locked nucleic acid (LNA) group). We assessed miRNA-939 levels in serum, kidneys and lungs using a reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase (sGC) were quantified using Western blotting. Serum nitric oxide (NO) levels were determined using the nitrate reductase method.</p><p><strong>Results: </strong>Compared to the sham group, the rats in the sepsis model group exhibited significantly elevated levels of miRNA-939 in serum, with distinct peaks at 12, 24, and 36 h post-sepsis induction. Similarly, the protein levels of iNOS and sGC (sGCα1 and sGCβ1 subunits) in kidneys and lungs were markedly higher in the sepsis group. Serum NO levels were also significantly elevated in the sepsis group compared to the sham group. Importantly, inhibition of miRNA-939 in the LNA group led to a significant reduction in the tissue levels of iNOS, sGCα1, sGCβ1, and serum NO within the NO/cGMP pathway, alongside mitigating inflammatory damage to kidneys and lungs.</p><p><strong>Conclusions: </strong>Inhibiting miRNA-939 significantly reduces the expression of iNOS, sGCα1, sGCβ1, and NO in the NO/cGMP pathway in CLP-exposed rats, thereby alleviating inflammatory organ damage in sepsis. These findings highlight the therapeutic potential of targeting miRNA-939 in the management of sepsis-induced organ dysfunction.</p>\",\"PeriodicalId\":12322,\"journal\":{\"name\":\"Folia histochemica et cytobiologica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Folia histochemica et cytobiologica\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.5603/fhc.101988\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia histochemica et cytobiologica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.5603/fhc.101988","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Mechanisms of alleviating sepsis-induced rat lung and kidney damage by inhibiting expression of miRNA-939.
Introduction: Sepsis, a life-threatening condition caused by a host response that goes out of control, leads to severe organ dysfunction. MicroRNA 939 (miRNA-939) plays a pivotal role in this process by post-transcriptionally regulating the mRNA expression of key enzymes in the NO/cGMP pathway. This pathway is crucial in the development of refractory hypotension and organ failure in sepsis. The aim of the study was to explore the effects of miRNA-939 on a caecum ligation puncture (CLP) rat model of sepsis in kidneys and lungs in order to elucidate its role in modulating the NO/cGMP pathway and related organ protection mechanisms.
Material and methods: To explore the effects of miRNA-939 on sepsis, we established three groups of rats: a sham surgery group, a sepsis model group, and an intervention group treated with LNA-antimiR targeting miRNA-939, which was administered via tail vein injection (the locked nucleic acid (LNA) group). We assessed miRNA-939 levels in serum, kidneys and lungs using a reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase (sGC) were quantified using Western blotting. Serum nitric oxide (NO) levels were determined using the nitrate reductase method.
Results: Compared to the sham group, the rats in the sepsis model group exhibited significantly elevated levels of miRNA-939 in serum, with distinct peaks at 12, 24, and 36 h post-sepsis induction. Similarly, the protein levels of iNOS and sGC (sGCα1 and sGCβ1 subunits) in kidneys and lungs were markedly higher in the sepsis group. Serum NO levels were also significantly elevated in the sepsis group compared to the sham group. Importantly, inhibition of miRNA-939 in the LNA group led to a significant reduction in the tissue levels of iNOS, sGCα1, sGCβ1, and serum NO within the NO/cGMP pathway, alongside mitigating inflammatory damage to kidneys and lungs.
Conclusions: Inhibiting miRNA-939 significantly reduces the expression of iNOS, sGCα1, sGCβ1, and NO in the NO/cGMP pathway in CLP-exposed rats, thereby alleviating inflammatory organ damage in sepsis. These findings highlight the therapeutic potential of targeting miRNA-939 in the management of sepsis-induced organ dysfunction.
期刊介绍:
"Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology.
"Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica".
"Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.