JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL
Objective. To explore the role of the c-Jun N-terminal kinase (JNK) signaling pathway in upregulated NGAL expression and its antiapoptotic mechanism in lipopolysaccharide (LPS)-mediated renal tubular epithelial cell injury. Methods. In vitro, HK-2 cells were divided into five groups (Con, LPS 1 h, L...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | International Journal of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/3980507 |
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| author | Mei Han Yuxia Pan Mengying Gao Junli Zhang Fan Wang |
| author_facet | Mei Han Yuxia Pan Mengying Gao Junli Zhang Fan Wang |
| author_sort | Mei Han |
| collection | DOAJ |
| description | Objective. To explore the role of the c-Jun N-terminal kinase (JNK) signaling pathway in upregulated NGAL expression and its antiapoptotic mechanism in lipopolysaccharide (LPS)-mediated renal tubular epithelial cell injury. Methods. In vitro, HK-2 cells were divided into five groups (Con, LPS 1 h, LPS 3 h, LPS 6 h, and LPS 12 h groups) based on the time of LPS (10 μM) treatment. NGAL and caspase-3 gene expression levels were detected by RT-PCR to assess dynamic changes. HK-2 cells were pretreated with SP600125 (20 μM) for 2 hours, followed by LPS (10 μM) stimulation for 3 hours. NGAL and caspase-3 gene expression levels were then determined. Results. NGAL mRNA was increased significantly within 6 hours, and caspase-3 mRNA was increased within 3 hours after treatment (P<0.05). Correlation analysis showed a high correlation between their expression (r = 0.448, P<0.05). After pretreatment with SP600125, mRNA expression of NGAL in the LPS group was inhibited, while that of caspase-3 was increased significantly. The NGAL mRNA expression level in the SB + LPS group was decreased significantly compared with that in the LPS group, but it was slightly higher than that in the SP group (∼1.5 times of that in the Con group). However, caspase-3 mRNA expression was increased significantly in the SB + LPS group (P<0.001) (3.5 times of that in the Con group). It also showed a significant increase compared with SP and LPS groups (P<0.001 vs. SB group; P<0.05 vs. LPS group). We also found that NGAL and caspase 3 proteins were increased significantly in LPS and SP + LPS groups, but SP600125 decreased the NGAL level by almost 35% and increased the caspase 3 level by 50% in the SP + LPS group compared with the LPS group (P<0.05). Conclusions. The JNK signaling pathway inhibits LPS-mediated apoptosis of renal tubular epithelial cells by upregulating NGAL. |
| format | Article |
| id | doaj-art-82dafa545d704dc08d8d616e5b90a39c |
| institution | Kabale University |
| issn | 2090-8040 2042-0099 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Inflammation |
| spelling | doaj-art-82dafa545d704dc08d8d616e5b90a39c2025-02-03T00:58:48ZengWileyInternational Journal of Inflammation2090-80402042-00992020-01-01202010.1155/2020/39805073980507JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGALMei Han0Yuxia Pan1Mengying Gao2Junli Zhang3Fan Wang4Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Hemopathy, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaObjective. To explore the role of the c-Jun N-terminal kinase (JNK) signaling pathway in upregulated NGAL expression and its antiapoptotic mechanism in lipopolysaccharide (LPS)-mediated renal tubular epithelial cell injury. Methods. In vitro, HK-2 cells were divided into five groups (Con, LPS 1 h, LPS 3 h, LPS 6 h, and LPS 12 h groups) based on the time of LPS (10 μM) treatment. NGAL and caspase-3 gene expression levels were detected by RT-PCR to assess dynamic changes. HK-2 cells were pretreated with SP600125 (20 μM) for 2 hours, followed by LPS (10 μM) stimulation for 3 hours. NGAL and caspase-3 gene expression levels were then determined. Results. NGAL mRNA was increased significantly within 6 hours, and caspase-3 mRNA was increased within 3 hours after treatment (P<0.05). Correlation analysis showed a high correlation between their expression (r = 0.448, P<0.05). After pretreatment with SP600125, mRNA expression of NGAL in the LPS group was inhibited, while that of caspase-3 was increased significantly. The NGAL mRNA expression level in the SB + LPS group was decreased significantly compared with that in the LPS group, but it was slightly higher than that in the SP group (∼1.5 times of that in the Con group). However, caspase-3 mRNA expression was increased significantly in the SB + LPS group (P<0.001) (3.5 times of that in the Con group). It also showed a significant increase compared with SP and LPS groups (P<0.001 vs. SB group; P<0.05 vs. LPS group). We also found that NGAL and caspase 3 proteins were increased significantly in LPS and SP + LPS groups, but SP600125 decreased the NGAL level by almost 35% and increased the caspase 3 level by 50% in the SP + LPS group compared with the LPS group (P<0.05). Conclusions. The JNK signaling pathway inhibits LPS-mediated apoptosis of renal tubular epithelial cells by upregulating NGAL.http://dx.doi.org/10.1155/2020/3980507 |
| spellingShingle | Mei Han Yuxia Pan Mengying Gao Junli Zhang Fan Wang JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL International Journal of Inflammation |
| title | JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL |
| title_full | JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL |
| title_fullStr | JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL |
| title_full_unstemmed | JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL |
| title_short | JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL |
| title_sort | jnk signaling pathway suppresses lps mediated apoptosis of hk 2 cells by upregulating ngal |
| url | http://dx.doi.org/10.1155/2020/3980507 |
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