Heat Shock Protein 47 and Renal Fibrogenesis

Le, Viet Thang; Taguchi, Takashi

doi:10.1159/000086043

Cited by 35 publications

(26 citation statements)

References 56 publications

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“…Previous in vivo and in vitro studies have convincingly shown that HSP47 plays an important role in the onset and progression of various fibrotic diseases, particularly those affecting the artery wall (24). HSP47 is localized in the endoplasmic reticulum of collagen-producing cells and is thought to be essential for the synthesis, processing, and secretion of pro-collagen molecules (17).…”

Section: Discussionmentioning

confidence: 99%

Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis

Sevin

Pignieri

Budelli

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Thromboxane A(2) and other eicosanoids such as isoprostanes contribute to vascular proliferation and atherosclerosis by binding to the thromboxane/prostaglandin endoperoxide receptors. The effects of terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, on aorta remodeling were evaluated in spontaneously hypertensive stroke-prone rats (SHRSPs), a model of severe hypertension, endothelial dysfunction, vascular inflammation, and cerebrovascular diseases. Male SHRSPs were allocated to three groups receiving a standard diet (n = 5) or a high-sodium permissive diet plus vehicle (n = 6) or plus terutroban (30 mg · kg(-1) · day(-1); n = 6). After 6 wk of dietary treatment, all of the animals were injected with bromodeoxyuridine and simultaneously euthanized for aorta collection. The aortic media thickness-to-lumen ratio significantly (P < 0.0001) increased in the salt-loaded rats compared with the rats fed a standard diet, whereas terutroban treatment completely prevented media thickening (P < 0.001). When compared with vehicle, terutroban was also effective in preventing cell proliferation in the media, as indicated by the reduced number of bromodeoxyuridine-positive (P < 0.0001) and proliferating cell nuclear antigen-positive cells (P < 0.0001). Severe fibrosis characterized by a significant accumulation of collagen and fibronectin in the vascular wall was observed in the vehicle-treated rats (P < 0.01) but was completely prevented by terutroban (P < 0.001). The latter also inhibited heat shock protein-47 (P < 0.01) and TGF-1β expression (P < 0.001), which were significantly increased by the high-salt diet. In conclusion, terutroban prevents the development of aorta hyperplasia and has beneficial effects on fibrotic processes by affecting TGF-β and heat shock protein-47 expression in SHRSPs. These findings provide mechanistic data supporting the beneficial effects of terutroban in preventing or retarding atherogenesis.

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Section: Discussionmentioning

confidence: 99%

Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis

Sevin

Pignieri

Budelli

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…6 During this process tubule cells loose epithelial features and convert to fibroblast-like cells. 3 This epithelial-mesenchymal transition (EMT) is paralleled for example by the expression of fibroblast-specific protein-1(FSP1), 13 heat shock protein 47 (HSP 47) 10,16,21 and a-smooth muscle actin (SMA). 31 In contrast, mesenchymal-epithelial transition (MET) plays an important role, when stem/progenitor cells are applied to support regeneration in acute or chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

et al. 2010

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Abstract-An increasing number of investigations is dealing with the repair of acute and chronic renal failure by the application of stem/progenitor cells. However, accurate data concerning the cell biological mechanisms controlling the process of regeneration are scarce. For that reason new implantation techniques, advanced biomaterials and morphogens supporting regeneration of renal parenchyma are under research. Special focus is directed to structural and functional features of the interface between generating tubules and the surrounding interstitial space. The aim of the present experiments was to investigate structural features of the interstitium during generation of tubules. Stem/ progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of a polyester fleece to create an artificial interstitium. Perfusion culture was performed for 13 days in chemically defined Iscove's Modified Dulbecco's Medium containing aldosterone (1 9 10 À7 M) as tubulogenic factor. Recordings of the artificial interstitium in comparison to the developing kidney were performed by morphometric analysis, scanning and transmission electron microscopy. The degree of differentiation was registered by immunohistochemistry. The data reveal that generated tubules are embedded in a complex network of fibers consisting of newly synthesized extracellular matrix proteins. Morphometric analysis further shows that the majority of tubules within the artificial interstitium develops in a surprisingly close distance between 5 and 25 lm to each other. The abundance of synthesized extracellular matrix acts obviously as a spacer keeping generated tubules in distance. For comparison, the same principle of construction is found in the developing parenchyma of the neonatal kidney. Most astonishingly, scanning electron microscopy reveals that the composition of interstitial matrix is not homogeneous but differs along a cortico-medullary axis of proceeding tubule development.Keywords-Tissue engineering, Perfusion culture, Kidney, Tubule, Artificial interstitium, Collagen type III. INTRODUCTIONRecovery from renal failure requires the replacement of injured tissue with new cells that restore epithelial integrity and functionality within tubules. An increasing number of papers is therefore dealing with strategies for repair of parenchyma by the help of stem/progenitor cells. 5,12 However, recent data show that an effective therapy is still far away from a widespread clinic application. Unsolved issues in renal tissue engineering are the concentration of stem/progenitor cells at the site of damage, their integration in a diseased environment, the process of differentiation into nephron-specific cells, and the spatial development of tubules within the kidney. 32 Part of actual research is focusing on cell biological mechanisms involved in the formation of tubules during regeneration. 4 Due to the spatial microarchitecture of the kidney experiments are frequently performed applying three-dimensional culture experiments in combination wi...

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“…TGF- β 1 is the core cytokine leading to the synthesis of ECM, which is responsible for mesangial fibrosis and hypertrophy under diabetic conditions [6]. The major components of the ECM proteins collagen types I–IV and their synthesis and immoderate deposition are consistently observed in multifarious renal disease processes affecting humans and experimental animals [7, 8]. …”

Section: Introductionmentioning

confidence: 99%

Tribbles 3 Regulates the Fibrosis Cytokine TGF-β1 through ERK1/2-MAPK Signaling Pathway in Diabetic Nephropathy

Zhang

Liu

et al. 2014

Journal of Immunology Research

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To reveal the expression and possible role of tribbles homolog 3 (TRB3) in the incidence of type 2 diabetic nephropathy, we used immunohistochemistry, real-time quantitative PCR, western blot analysis, and enzyme-linked immunosorbent assay (ELISA) to study the expression of TRB3, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK), transforming growth factor β1 (TGF-β1), and collagen type IV in kidneys of db/db diabetic mice and in murine renal mesangial cells stimulated with high glucose. The expression of TRB3, TGF-β1, and collagen type IV was increased in kidneys of db/db diabetic mice. TGF-β1 and collagen type IV regulated by high glucose through ERK1/2 MAPK were downregulated by silencing TRB3 in renal mesangial cells. TRB3 may be involved in diabetic nephropathy by regulating the fibrosis cytokine TGF-β1 and collagen type IV through the ERK1/2 MAPK signaling pathway.

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Heat Shock Protein 47 and Renal Fibrogenesis

Cited by 35 publications

References 56 publications

Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis

Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

Tribbles 3 Regulates the Fibrosis Cytokine TGF-β1 through ERK1/2-MAPK Signaling Pathway in Diabetic Nephropathy

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