title: Pituitary adenylate cyclase-activating polypeptide protects glomerular podocytes from inflammatory injuries.
abstract: 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.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kuno
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Onishi
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ishibashi
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Okabe
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Shoji
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hattori
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaga
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Harukiyo
authors.initials: H
authors.lastname: Kawamura
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan ; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D018932:Chemokine CCL2 / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D017868:Cyclic AMP-Dependent Protein Kinases
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