Smooth-muscle calponin in mesangial cells: regulation of expression and a role in suppressing glomerulonephritis.
The basic or h1 calponin gene, which encodes an actin-binding protein involved in the regulation of smooth-muscle shortening velocity, is known to be a smooth-muscle differentiation-specific gene. It was found that basic calponin was expressed by cultured mesangial cells and localized along the actin filaments. Among the growth factors involved in the mesangial cell pathophysiology, including platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1), TNF-alpha potently downregulates basic calponin expression in both the mRNA and protein levels, whereas TGF-beta1 upregulates the calponin expression. PDGF-BB also reduced its mRNA expression. The half-life of basic calponin mRNA was determined to be similar between TNF-alpha-treated and -untreated mesangial cells, whereas cell transfection assays that used a luciferase reporter gene construct containing the functional basic calponin promoter showed that TNF-alpha and PDGF-BB reduced the transcriptional activity. Because stimulation with TNF-alpha and PDGF-BB was associated with mesangial cell proliferation, basic calponin may play a role in the suppression of mesangial cell proliferation. Treatment with anti-glomerular basement membrane antibody in calponin knockout mice induced more severe nephritis than in wild type mice, as judged from an increase in the urinary protein excretion, glomerular cellularity, and number of proliferating cell nuclear antigen-positive cells in glomerulus. These results suggest that basic calponin expression may serve as one of the intrinsic regulators of glomerular nephritis. Elucidation of the molecular mechanisms for regulation of the basic calponin expression in mesangial cells may improve the understanding of the molecular basis and pathogenesis of the glomerular response to injury.
Sugenoya
Youichi
Y
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Yoshimura
Ashio
A
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Yamamura
Hisako
H
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Inui
Kiyoko
K
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Morita
Hiroyuki
H
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Yamabe
Hideaki
H
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Ueki
Noboru
N
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Ideura
Terukuni
T
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Takahashi
Katsuhito
K
*Department of Medicine and Pathophysiology, Division of Nephrology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan; Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan; Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan; Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism* / Q000473:pathology*; D000077214:Becaplermin; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008840:Microfilament Proteins; D009130:Muscle, Smooth / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000502:physiology; D000096985:Calponins
D000077214:Becaplermin; D002135:Calcium-Binding Proteins; D006133:Growth Substances; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000096985:Calponins