title: A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.
abstract: Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, 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, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Akimoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, 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, Chiba, 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, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, 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, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Yokohama Rosai hospital, Yokohama, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tsurutani
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ide
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Ide
authors.affiliation: Eastern Chiba Medical Center, Chiba, 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, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Yu-karigaoka Tokuyama Clinic, Chiba, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.affiliation: Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology, Uppsala Universitet, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.|Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
mesh_terms: D000419:Albuminuria / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000276:immunology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013311:Streptozocin
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D039961:Semaphorins; C569384:semaphorin 3G, human; C505763:semaphorin 3G, mouse; D013311:Streptozocin