Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB
Objective. At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms. Methods. The in vitro and in vivo models of SAKI were est...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Applied Bionics and Biomechanics |
| Online Access: | http://dx.doi.org/10.1155/2022/1790104 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849682903483547648 |
|---|---|
| author | Shilei Zhao Lei Cui Xiufeng Zheng Ying Ji Chengyuan Yu |
| author_facet | Shilei Zhao Lei Cui Xiufeng Zheng Ying Ji Chengyuan Yu |
| author_sort | Shilei Zhao |
| collection | DOAJ |
| description | Objective. At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms. Methods. The in vitro and in vivo models of SAKI were established using lipopolysaccharide (LPS). Mel was injected intraperitoneally at 60 mg/kg into male C57BL/6 mice 4 hours before LPS injection (10 mg/kg). The HK-2 cells were treated with LPS (1 μg/mL) and Mel (40 μM). The renal function and renal pathological changes as well as renal inflammation and apoptosis were detected in SAKI mice. The inflammation and apoptosis of HK-2 cells induced by LPS were also detected. Results. The treatment of Mel significantly decreased the elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in SAKI mice. In addition, the results of HE staining suggested that Mel significantly reduced kidney damage in SAKI mice. Consistently, Mel reduced the expression of LPS-induced kidney injury markers (NGAL and KIM-1). Moreover, LPS induced the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the kidney, which can be reduced by Mel. Furthermore, Mel effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the kidneys of SAKI mice. Mechanistically, Mel inhibited the phosphorylation of P65 but induced the phosphorylation of AKT and the expression of glycoprotein B of nonmetastatic melanoma (GPNMB). However, knocking down GPNMB can eliminate the anti-inflammatory and antiapoptotic effects of Mel. Conclusion. Mel alleviated sepsis-induced kidney injury by inhibiting kidney inflammation and apoptosis via upregulating GPNMB. |
| format | Article |
| id | doaj-art-ca6197fb129e4528aa4e2fbdd49337f6 |
| institution | DOAJ |
| issn | 1754-2103 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Applied Bionics and Biomechanics |
| spelling | doaj-art-ca6197fb129e4528aa4e2fbdd49337f62025-08-20T03:24:03ZengWileyApplied Bionics and Biomechanics1754-21032022-01-01202210.1155/2022/1790104Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMBShilei Zhao0Lei Cui1Xiufeng Zheng2Ying Ji3Chengyuan Yu4Department of NephrologyDepartment of NephrologyDepartment of CardiologyDepartment of NephrologyDepartment of GerontologyObjective. At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms. Methods. The in vitro and in vivo models of SAKI were established using lipopolysaccharide (LPS). Mel was injected intraperitoneally at 60 mg/kg into male C57BL/6 mice 4 hours before LPS injection (10 mg/kg). The HK-2 cells were treated with LPS (1 μg/mL) and Mel (40 μM). The renal function and renal pathological changes as well as renal inflammation and apoptosis were detected in SAKI mice. The inflammation and apoptosis of HK-2 cells induced by LPS were also detected. Results. The treatment of Mel significantly decreased the elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in SAKI mice. In addition, the results of HE staining suggested that Mel significantly reduced kidney damage in SAKI mice. Consistently, Mel reduced the expression of LPS-induced kidney injury markers (NGAL and KIM-1). Moreover, LPS induced the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the kidney, which can be reduced by Mel. Furthermore, Mel effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the kidneys of SAKI mice. Mechanistically, Mel inhibited the phosphorylation of P65 but induced the phosphorylation of AKT and the expression of glycoprotein B of nonmetastatic melanoma (GPNMB). However, knocking down GPNMB can eliminate the anti-inflammatory and antiapoptotic effects of Mel. Conclusion. Mel alleviated sepsis-induced kidney injury by inhibiting kidney inflammation and apoptosis via upregulating GPNMB.http://dx.doi.org/10.1155/2022/1790104 |
| spellingShingle | Shilei Zhao Lei Cui Xiufeng Zheng Ying Ji Chengyuan Yu Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB Applied Bionics and Biomechanics |
| title | Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB |
| title_full | Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB |
| title_fullStr | Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB |
| title_full_unstemmed | Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB |
| title_short | Meloxicam Alleviates Sepsis-Induced Kidney Injury by Suppression of Inflammation and Apoptosis via Upregulating GPNMB |
| title_sort | meloxicam alleviates sepsis induced kidney injury by suppression of inflammation and apoptosis via upregulating gpnmb |
| url | http://dx.doi.org/10.1155/2022/1790104 |
| work_keys_str_mv | AT shileizhao meloxicamalleviatessepsisinducedkidneyinjurybysuppressionofinflammationandapoptosisviaupregulatinggpnmb AT leicui meloxicamalleviatessepsisinducedkidneyinjurybysuppressionofinflammationandapoptosisviaupregulatinggpnmb AT xiufengzheng meloxicamalleviatessepsisinducedkidneyinjurybysuppressionofinflammationandapoptosisviaupregulatinggpnmb AT yingji meloxicamalleviatessepsisinducedkidneyinjurybysuppressionofinflammationandapoptosisviaupregulatinggpnmb AT chengyuanyu meloxicamalleviatessepsisinducedkidneyinjurybysuppressionofinflammationandapoptosisviaupregulatinggpnmb |