Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries
Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease; however, there are few treatment options. Inflammation plays a crucial role in the initiation and/or progression of DN. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide, which was originally isolate...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/727152 |
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| author | Kenichi Sakamoto Kyoko Kuno Minoru Takemoto Peng He Takahiro Ishikawa Shunichiro Onishi Ryoichi Ishibashi Emiko Okabe Mayumi Shoji Akiko Hattori Masaya Yamaga Kazuki Kobayashi Harukiyo Kawamura Hirotake Tokuyama Yoshiro Maezawa Koutaro Yokote |
| author_facet | Kenichi Sakamoto Kyoko Kuno Minoru Takemoto Peng He Takahiro Ishikawa Shunichiro Onishi Ryoichi Ishibashi Emiko Okabe Mayumi Shoji Akiko Hattori Masaya Yamaga Kazuki Kobayashi Harukiyo Kawamura Hirotake Tokuyama Yoshiro Maezawa Koutaro Yokote |
| author_sort | Kenichi Sakamoto |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease; however, there are few treatment options. Inflammation plays a crucial role in the initiation and/or progression of DN. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide, which was originally isolated from the ovine hypothalamus and reportedly has diverse biological functions. It has been reported that PACAP has renoprotective effects in different models of kidney pathology. However, the specific cell types within the kidney that are protected by PACAP have not yet been reported. In this study, we localized VPAC1, one of the PACAP receptors, to glomerular podocytes, which also reportedly has crucial roles not only in glomerular physiology but also in pathology. PACAP was effective in the downregulation of proinflammatory cytokines, such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-6, which had been induced by the activation of toll-like receptor (TLR) with lipopolysaccharide. PACAP also had downregulated the expression of MCP-1 through the protein kinase A signaling pathway; this led to the attenuation of the activation of extracellular signal-regulated kinase and nuclear factor-kappa B signaling. Our results suggested that PACAP could be a possible treatment option for DN through the use of anti-inflammation effects on glomerular podocytes. |
| format | Article |
| id | doaj-art-d66ce7237b00420d896d37d762cf7d46 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-d66ce7237b00420d896d37d762cf7d462025-02-03T06:08:25ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/727152727152Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory InjuriesKenichi Sakamoto0Kyoko Kuno1Minoru Takemoto2Peng He3Takahiro Ishikawa4Shunichiro Onishi5Ryoichi Ishibashi6Emiko Okabe7Mayumi Shoji8Akiko Hattori9Masaya Yamaga10Kazuki Kobayashi11Harukiyo Kawamura12Hirotake Tokuyama13Yoshiro Maezawa14Koutaro Yokote15Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, JapanDiabetic nephropathy (DN) is a leading cause of end-stage kidney disease; however, there are few treatment options. Inflammation plays a crucial role in the initiation and/or progression of DN. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide, which was originally isolated from the ovine hypothalamus and reportedly has diverse biological functions. It has been reported that PACAP has renoprotective effects in different models of kidney pathology. However, the specific cell types within the kidney that are protected by PACAP have not yet been reported. In this study, we localized VPAC1, one of the PACAP receptors, to glomerular podocytes, which also reportedly has crucial roles not only in glomerular physiology but also in pathology. PACAP was effective in the downregulation of proinflammatory cytokines, such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-6, which had been induced by the activation of toll-like receptor (TLR) with lipopolysaccharide. PACAP also had downregulated the expression of MCP-1 through the protein kinase A signaling pathway; this led to the attenuation of the activation of extracellular signal-regulated kinase and nuclear factor-kappa B signaling. Our results suggested that PACAP could be a possible treatment option for DN through the use of anti-inflammation effects on glomerular podocytes.http://dx.doi.org/10.1155/2015/727152 |
| spellingShingle | Kenichi Sakamoto Kyoko Kuno Minoru Takemoto Peng He Takahiro Ishikawa Shunichiro Onishi Ryoichi Ishibashi Emiko Okabe Mayumi Shoji Akiko Hattori Masaya Yamaga Kazuki Kobayashi Harukiyo Kawamura Hirotake Tokuyama Yoshiro Maezawa Koutaro Yokote Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries Journal of Diabetes Research |
| title | Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries |
| title_full | Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries |
| title_fullStr | Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries |
| title_full_unstemmed | Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries |
| title_short | Pituitary Adenylate Cyclase-Activating Polypeptide Protects Glomerular Podocytes from Inflammatory Injuries |
| title_sort | pituitary adenylate cyclase activating polypeptide protects glomerular podocytes from inflammatory injuries |
| url | http://dx.doi.org/10.1155/2015/727152 |
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