Based on the relationship of macrophages-myofibroblasts, the pathogenesis of renal fibrosis and its therapeutic strategies

• Project/Area Number: 18380188
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: Osaka Prefecture University
• Principal Investigator: YAMATE Jyoji Osaka Prefecture University, 生命環境科学研究科, 教授 (50150115)
• Co-Investigator(Kenkyū-buntansha): KUWAMURA Mitsuru 大阪府立大学, 生命環境科学研究科, 准教授 (20244668) ; TAKENAKA Shigeo 大阪府立大学, 生命環境科学研究科, 准教授 (10280067) ; IWASAKI Tadashi 大阪府立大学, 生命環境科学研究科, 助教 (70336808)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥17,450,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,250,000); Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2006: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: 病態 / 病理発生 / 応用動物学 / 腎線維化モデル / マクロファージ / 筋線維芽細胞 / 腎線維化 / 骨髄幹細胞 / 血管新生 / Thy-1 / 肝線維化 / 創傷治癒線維化 / シクロオキシゲー / EP4 / 抗原提示マクロファージ / MCP-1 / 細胞骨格 / 細胞モデル

Research Abstract

To clarify the pathogenesis of renal fibrosis leading to chronic renal disease, functional properties of macrophages and myofibroblasts appearing in kidney injured tissues were investigated pathologically. It was found that heterogeneous macrophages appeared, and that then factors produced by macrophages could induce myofibroblasts. Inhibition of macrophage functions may improve renal fibrosis. Additionally, hepatic fibrosis and wound healing fibrosis were analyzed comparative-pathologically.

Research Products

• [Journal Article] Involvement of endogenous prostaglandin E2 in tubular epithelial regeneration through inhibition of apoptosis and epithelial-mesenchymal transition in cisplatin-induced rat renal lesions. (2010)
  • Author(s): Yamamoto E, Izawa T, Vetnizah J, Kuwamura M, Sugiura K, Takeuchi T, Yamate J
  • Journal Title: Histol Histopathol (in press)
  • Peer Reviewed
• [Journal Article] The kinetics and distribution of different macrophage populations in the developing rat skin. (2010)
  • Author(s): Vetnizah J, Izawa T, Yamamoto E, Kuwamura M, Yamate J
  • Journal Title: Histol Histopathol (in press)
  • Peer Reviewed
• [Journal Article] Thy-1 expression mesenchymal cells in rat nephrogenesis, in correlation with cells immunoreactive for α-smooth muscle actin and vimentin. (2010)
  • Author(s): Yuasa T, Izawa T, Kuwamura M, Yamate J
  • Journal Title: J Toxicol Pathol (in press)
  • NAID: 10030978474
  • Peer Reviewed
• [Journal Article] Involvement of endogenous prostaglandin E2 in tubular epithelial regeneration through inhibition of apoptosis and epithelial-mesenchymal transition in cisplatin-induced rat renal lesions (2010)
  • Author(s): Yamamoto, E, et al.
  • Journal Title: Histol.Histopathol. (in press)
  • Peer Reviewed
• [Journal Article] Participation of functionally-different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic injury. (2009)
  • Author(s): Mori Y, Izawa T, Takenaka S, Kuwamura M, Yamate J
  • Journal Title: Toxicol Pathol 37(4) Pages: 463-473
  • Peer Reviewed
• [Journal Article] Macrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro. (2009)
  • Author(s): Yamate J, Ishimine S, Izawa T, Kumagai D, Kuwamura M
  • Journal Title: Histol Histopathol 24(1) Pages: 13-24
  • Peer Reviewed
• [Journal Article] Participation of functionally different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetoamide-induced rat hepatic injury (2009)
  • Author(s): Mori Y, et al.
  • Journal Title: Toxicol Pathol 37 Pages: 463-473
  • Peer Reviewed
• [Journal Article] Identifination of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database (2009)
  • Author(s): Kondo C, et al.
  • Journal Title: Toxicology 265 Pages: 15-26
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 山手丈至(分担執筆)
  • Journal Title: 産学官連携の研究開発:第9章;獣医学が目指す癌撲滅に向けた基礎研究-ラット腫瘍モデルの確立と応用-(中央経済社) Pages: 113-135
• [Journal Article] Participation of functionally-different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic injury (2009)
  • Author(s): Mori Y, Izawa T, Takenaka S, Kuwamura M and Yamate J.
  • Journal Title: Toxicol Pathol (in press)
  • Peer Reviewed
• [Journal Article] Macrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro (2009)
  • Author(s): Yamate J, Ishimine S, Izawa T, Kumagai D and Kuwamura M.
  • Journal Title: Histol Histopathol 24(1) Pages: 13-24
  • Peer Reviewed
• [Journal Article] Macrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro. (2009)
  • Author(s): Yamate J, et al.
  • Journal Title: Histol. Histopathol. 24 Pages: 13-24
  • Peer Reviewed
• [Journal Article] Effect of polyphenol-containing azuki bean (Vigna angularis) extract on blood pressure elevation and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats. (2008)
  • Author(s): Sato S, Mukai Y, Yamate J, Kato J, Kurasaki M, Hatai A, Sagai M
  • Journal Title: Clin Exp Pharmacol Physiol 35(1) Pages: 43-49
  • Peer Reviewed
• [Journal Article] Effect of polyphenol-containing azuki bean (Vigna angularis) extract on blood pressure elevation and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats (2008)
  • Author(s): Sato S, Mukai Y, Yamate J, Kato J, Kurasaki M, Hatai A and Sagai M.
  • Journal Title: Clin Exp Pharmacol Physiol 35(1) Pages: 43-49
  • Peer Reviewed
• [Journal Article] Time course of the change and amelioration of nedaplatin-induced nephrotoxicity in rats (2008)
  • Author(s): Uehara T, et al.
  • Journal Title: J. Appl. Toxicol. 28 Pages: 388-398
  • Peer Reviewed
• [Journal Article] Heterogeneity of macrophage populations and myofibroblasts appearing in rat renal interstitial fibrosis (2007)
  • Author(s): Yamate J
  • Journal Title: J Toxicol Pathol 20(4) Pages: 185-195
  • Peer Reviewed
• [Journal Article] Adipogenic, osteogenic and myofibrogenic differentiations of a rat malignant fibrous histiocytoma (MFH)-derived cell line, and a relationship of MFH cells with embryonal mesenchymal, perivascular and bone marrow stem cells. (2007)
  • Author(s): Yamate J, Ogata K, Yuasa T, Kuwamura M, Takenaka S, Kumagai D, Itoh K, LaMarre J
  • Journal Title: Eur J Cancer 43(18) Pages: 2747-2756
  • Peer Reviewed
• [Journal Article] Heterogeneity of macrophage populations and myofibroblasts appearing in rat renal interstitial fibrosis (review) (2007)
  • Author(s): Yamate J.
  • Journal Title: J Toxicol Pathol. 20(4) Pages: 185-195
  • Peer Reviewed
• [Journal Article] Adipogenic, osteogenic and myofibrogenic differentiations of a rat malignant fibrous histiocytoma (MFH)-derived cell line, and a relationship of MFH cells with embryonal mesenchymal, perivascular and bone marrow stem cells (2007)
  • Author(s): Yamate J, Ogata K, Yuasa T, Kuwamura M, Takenaka S, Kumagai D, Itoh K and LaMarre J.
  • Journal Title: Eur J Cancer. 43(18) Pages: 2747-2756
  • Peer Reviewed
• [Journal Article] Heterogeneity of macrophage populations and myofibroblasts appearing in ratrenal interstitial fibrosis. (2007)
  • Author(s): Yarnate J, et. al.
  • Journal Title: J. Toxicol. Pathol. 20 Pages: 185-195
  • Peer Reviewed
• [Journal Article] Adipogenic, osteogenic and myofibrogenic differentiations of a rat malignant fibrous histiocytoma (MFH)-derived cell line, and a relationship of MFH cells with embonal mesenchmal, erivascular and bone marrow stem cells. (2007)
  • Author(s): Yamate J, et. al.
  • Journal Title: Eur. J. Cancer. 43 Pages: 2747-2756
  • Peer Reviewed
• [Journal Article] Urinary metabolic fingerprinting for thioacetamide-induced rat acute hepatic injury using fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS), with reference to detection of potential biomarkers for heatotoxicity (2007)
  • Author(s): Hasegawa M, et. al.
  • Journal Title: Toxicol Pathol. 35 Pages: 570-575
  • Peer Reviewed
• [Journal Article] characterization of a rat subcutaneous malignant fibrous histiocytoma and its tumor lines, with reference to histiocytic features (2007)
  • Author(s): Yamate J., et al.
  • Journal Title: Vet. Pathol. 44 Pages: 151-160
• [Presentation] マクロファージ-筋線維芽細胞を基軸にした腎間質線維化の病理発生 (2010)
  • Author(s): 山手丈至, 矢野遼, 村井文, 山本絵美, 湯浅隆宏, 栗林正伯, 桑村充
  • Organizer: 第26回日本毒性病理学会学術集会
  • Place of Presentation: 金沢
• [Presentation] Thioacetoamide誘発肝障害モデルにおけるHeat Shock Protein 25の発現とマクロファージの関連 (2010)
  • Author(s): 藤澤可恵, 土谷紀子, 増野功一, 山本絵美, 丸山敏之, 桑村充, 山手丈至, 鳥井幹則
  • Organizer: 第26回日本毒性病理学会学術集会
  • Place of Presentation: 金沢
• [Presentation] ラット腎発生過程におけるThy-1免疫陽性間葉系細胞の動態, 特にα-平滑筋アクチン及びvimentin陽性細胞との関連 (2010)
  • Author(s): 湯浅隆宏, 井澤武史, 桑村充, 山手丈至
  • Organizer: 第26回日本毒性病理学会学術集会
  • Place of Presentation: 金沢
• [Presentation] Immunohistochemical analyses of myofibroblasts appearing in rat excisional wound healing. (2009)
  • Author(s): Vetnizah J, 井澤武史, 村井文, 山本絵美, 桑村充, 山手丈至
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: 鳥取
• [Presentation] Immunohistochemical analyses in the developing rat live, particularly macrophages, mesenchymal stellate cells and bile duct epithelia. (2009)
  • Author(s): Golbar HM, 井澤武史, 村井文, 桑村充, 山手丈至
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: 鳥取
• [Presentation] シスプラチン誘発ラット腎線維化病変に発現する骨形成因子 (2009)
  • Author(s): 矢野遼, 井澤武史, 澤本修, 桑村充, 山手丈至
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: 鳥取
• [Presentation] Macrophage appearance and monocyte chemoattractant protein-1 in thioacetamide-induced rat hepatic injury. (2008)
  • Author(s): Yamate J, Mori Y, zawa T, Takenaka S, Kuwamura M
  • Organizer: The 27th Annual Meeting of the Society of Toxicologic Pathology (STP)
  • Place of Presentation: San Francisco
• [Presentation] Macrophage appearance and monocyte chemoattractant protein-1 in thioacetamide-induced rat hepatic injury (2008)
  • Author(s): Yamate J, Mori Y, zawa T, Takenaka S and Kuwamura M.
  • Organizer: The 27th Annual Meeting of the Society of Toxicologic Pathology (STP)
  • Place of Presentation: San Francisco
• [Presentation] Macrophage appearance and monocyte chemoattractant protein-1 in thioacetamide-induced rat hepatic injury (2008)
  • Author(s): Yamate J, et al.
  • Organizer: The 27th Annual Meeting of the Society of Toxicologic Pathology (STP)
  • Place of Presentation: アメリカ サンフランシスコ
• [Presentation] 腎線維化の進展機序:マクロファージと筋線維芽細胞の役割、ならびに実験モデルを用いたACE阻害剤の効果 (2007)
  • Author(s): 山手 丈至
  • Organizer: 第28回動物臨床医学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2007-11-17
• [Presentation] 慢性腎不全猫に対するACE阻害剤の具体的な使い方-腎間質線維化の面から-腎線維化の進展機序:マクロファージと筋線維芽細胞の役割, ならびに実験モデルを用いたACE阻害剤の効果 (2007)
  • Author(s): 山手丈至
  • Organizer: 第28回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] シスプラチン誘発急性腎傷害モデルにおけるCOX-2の発現と再生尿細管との係わり (2007)
  • Author(s): 山本絵美, 山手丈至, 井澤武史, 桑村充, 小谷猛夫
  • Organizer: 第143回日本獣医学会学術集会
  • Place of Presentation: つくば
• [Presentation] 慢性腎不全猫に対するACE阻害剤の具体的な使い方-腎間質線維化の面から-腎線維化の進展機序 : マクロファージと筋線維芽細胞の役割, ならびに実験モデルを用いたACE阻害剤の効果 (2007)
  • Author(s): 山手丈至
  • Organizer: 第28回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] ラットの腎線維化と腎発生におけるThy-1発現細胞の分布と特性解析 (2006)
  • Author(s): 湯浅隆宏, 山手丈至, 井澤武史, 桑村充, 小谷猛夫
  • Organizer: 第142回日本獣医学会学術集会
  • Place of Presentation: 山口
• [Presentation] Renal interstitial fibrosis in neonatal rats induced by cisplatin. (2006)
  • Author(s): Yamate Y, Machida Y, Kuwamura M, Kotani T
  • Organizer: The 24th European Society of Veterinary Pathology (ESVP)
  • Place of Presentation: Edinburgh
• [Presentation] Renal interstitial fibrosis in neonatal rats induced by cisplatin (2006)
  • Author(s): Yamate Y, Machida Y, Kuwamura M, Kotani T.
  • Organizer: The 24th European Society of Veterinary Pathology (ESVP)
  • Place of Presentation: Edinburgh
• [Book] 産学官連携の研究開発:第9章;獣医学が目指す癌撲滅に向けた基礎研究-ラット腫瘍モデルの確立と応用- (2009)
  • Author(s): 山手丈至(分担執筆)
  • Publisher: 中央経済社
• [Remarks] 山手丈至.腎線維化の病理発生:2009年10月27日.大阪府此花区住友化学株式会社安全性研究所社内セミナー
• [Remarks] 山手丈至.慢性腎臓病の病理学的進展機序:特にマクロファージ-筋線維芽細胞を基軸とした病態解析と治療法の探索. 2009年10月4日.日本獣医臨床病理学会2009年シンポジウム.大阪府立大学りんくうキャンパス
• [Remarks] 山手丈至.ラット腫瘍モデルの開発と生命科学の基礎研究に向けた応用性の探索と実用化. 2008年7月2日.第7回国際バイオフォーラム.東京ビックサイト
• [Remarks] 山手丈至.ラット腫瘍モデルの開発と生命科学の基礎研究に向けた応用性と実用化. 2008年7月11日.次世代医療システムフォーラム2008.大阪堺商工会議所
• [Remarks] 山手丈至.肝臓における線維化の病理発生. 2007年7月5日.徳島県鳴門大塚製薬工業株式会社
• [Remarks] 山手丈至.ラット腫瘍モデルの確立と応用:特に,線維化(腎線維化・肝硬変)の病理発生に向けた応用性の探索. 2007年6月26日.麻布大学生物科学総合研究所
• [Remarks] 山手丈至. 肝臓における線維化の病理発生. 2007 年7 月5 日. 徳島県 鳴門 大塚製薬工業株式会社
• [Remarks] 山手丈至. ラット腫瘍モデルの確立と応用:特に, 線維化(腎線維化・肝硬変)の病理発生に向けた応用性の探索. 2007 年6 月26日. 麻布大学 生物科学総合研究所