Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway
Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This stu...
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Elsevier
2025-01-01
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| Series: | Immunobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298524000809 |
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| author | Min Li Wenjia Tong Chao Dai Guoping Lu Danqun Jin Fang Deng |
| author_facet | Min Li Wenjia Tong Chao Dai Guoping Lu Danqun Jin Fang Deng |
| author_sort | Min Li |
| collection | DOAJ |
| description | Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition. |
| format | Article |
| id | doaj-art-ebfd17e0621b46e982191bd8348d32ca |
| institution | Kabale University |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Immunobiology |
| spelling | doaj-art-ebfd17e0621b46e982191bd8348d32ca2025-01-27T04:21:41ZengElsevierImmunobiology0171-29852025-01-012301152862Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathwayMin Li0Wenjia Tong1Chao Dai2Guoping Lu3Danqun Jin4Fang Deng5Department of Pediatric Nephrology, Children's Hospital of Anhui Medical University, Hefei, China; Department of Pediatric Nephrology, Anhui Provincial Children's Hospital, Hefei, ChinaDepartment of Pediatric Nephrology, Children's Hospital of Anhui Medical University, Hefei, China; Department of Pediatric Nephrology, Anhui Provincial Children's Hospital, Hefei, ChinaDepartment of Pediatric Intensive Care Unit, Children's Hospital of Anhui Medical University, Hefei, China; Department of Pediatric Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, ChinaDepartment of Pediatric Intensive Care Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Pediatric Intensive Care Unit, Children's Hospital of Anhui Medical University, Hefei, China; Department of Pediatric Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, China; Corresponding author at: Department of Pediatric Intensive Care Unit, Children's Hospital of Anhui Medical University, No. 39 Wangjiang East Road, Hefei, China.Department of Pediatric Nephrology, Children's Hospital of Anhui Medical University, Hefei, China; Department of Pediatric Nephrology, Anhui Provincial Children's Hospital, Hefei, China; Corresponding author at: Department of Pediatric Nephrology, Children's Hospital of Anhui Medical University, No. 39 Wangjiang East Road, Hefei, China.Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.http://www.sciencedirect.com/science/article/pii/S0171298524000809Sepsis-induced acute kidneyPSMB8NF-κBInflammationApoptosis |
| spellingShingle | Min Li Wenjia Tong Chao Dai Guoping Lu Danqun Jin Fang Deng Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway Immunobiology Sepsis-induced acute kidney PSMB8 NF-κB Inflammation Apoptosis |
| title | Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway |
| title_full | Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway |
| title_fullStr | Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway |
| title_full_unstemmed | Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway |
| title_short | Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway |
| title_sort | downregulation of the immunoproteasome subunit psmb8 attenuates sepsis associated acute kidney injury through the nf κb pathway |
| topic | Sepsis-induced acute kidney PSMB8 NF-κB Inflammation Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0171298524000809 |
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