SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells
Background. Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB sig...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/1685194 |
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| author | Wei Huang Yaling Liang Jianhua Dong Luping Zhou Chenlin Gao Chunxia Jiang Meijuan Chen Yang Long Yong Xu |
| author_facet | Wei Huang Yaling Liang Jianhua Dong Luping Zhou Chenlin Gao Chunxia Jiang Meijuan Chen Yang Long Yong Xu |
| author_sort | Wei Huang |
| collection | DOAJ |
| description | Background. Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined. Methods. Rat glomerular mesangial cells (GMCs) were stimulated by high glucose; siRNA was constructed to silence the expression of PIASy; the expression of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-κB signaling components was analyzed by Western blot; the interaction between IKKγ and SUMO proteins was detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP-1 and IL-6 was assayed by ELISA. Results. High glucose significantly upregulated the expression of PIASy, SUMO1, and SUMO2/3 in a dose- and time-dependent manner (P<0.05), induced the phosphorylation and sumoylation of IKKγ (P<0.05), and then triggered NF-κB signaling whereas MCP-1 and IL-6 were released from GMCs (P<0.05). Moreover, these high glucose-induced effects were observably reversed by siRNA-mediated knockdown of PIASy (P<0.05). Conclusion. The SUMO E3 ligase PIASy mediates high glucose-induced activation of NF-κB inflammatory signaling, suggesting that PIASy may be a potential therapeutic target of DN. |
| format | Article |
| id | doaj-art-cb8db8f4a5c94e638867347618d2afcd |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-cb8db8f4a5c94e638867347618d2afcd2025-08-20T03:23:37ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/16851941685194SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial CellsWei Huang0Yaling Liang1Jianhua Dong2Luping Zhou3Chenlin Gao4Chunxia Jiang5Meijuan Chen6Yang Long7Yong Xu8Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The People’s Hospital of Leshan, Leshan, Sichuan 614000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Geratology, The People’s Hospital of Leshan, Leshan, Sichuan 614000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaBackground. Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined. Methods. Rat glomerular mesangial cells (GMCs) were stimulated by high glucose; siRNA was constructed to silence the expression of PIASy; the expression of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-κB signaling components was analyzed by Western blot; the interaction between IKKγ and SUMO proteins was detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP-1 and IL-6 was assayed by ELISA. Results. High glucose significantly upregulated the expression of PIASy, SUMO1, and SUMO2/3 in a dose- and time-dependent manner (P<0.05), induced the phosphorylation and sumoylation of IKKγ (P<0.05), and then triggered NF-κB signaling whereas MCP-1 and IL-6 were released from GMCs (P<0.05). Moreover, these high glucose-induced effects were observably reversed by siRNA-mediated knockdown of PIASy (P<0.05). Conclusion. The SUMO E3 ligase PIASy mediates high glucose-induced activation of NF-κB inflammatory signaling, suggesting that PIASy may be a potential therapeutic target of DN.http://dx.doi.org/10.1155/2017/1685194 |
| spellingShingle | Wei Huang Yaling Liang Jianhua Dong Luping Zhou Chenlin Gao Chunxia Jiang Meijuan Chen Yang Long Yong Xu SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells Mediators of Inflammation |
| title | SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells |
| title_full | SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells |
| title_fullStr | SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells |
| title_full_unstemmed | SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells |
| title_short | SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells |
| title_sort | sumo e3 ligase piasy mediates high glucose induced activation of nf κb inflammatory signaling in rat mesangial cells |
| url | http://dx.doi.org/10.1155/2017/1685194 |
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