Local macrophage and myofibroblast proliferation in progressive renal injury in the rat remnant kidney

Yang, Niansheng; Wu, Linlin; Nikolic-Paterson, David J.; Ng, Yee Yung; Wu, Yang Chang; Mu, Wei; Gilbert, Richard E.; Cooper, Mark E.; Atkins, Robert C.; Lan, Hui‐Yao

doi:10.1093/ndt/13.8.1967

Cited by 89 publications

(50 citation statements)

References 2 publications

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“…40 CTGF, PDGF and TGF-␤ probably all interact in inducing proliferation of these cells. Both TGF-␤ and PDGF can induce the transformation of fibroblasts into myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…9,28,38 Contraction of the local extracellular matrix mediated by myofibroblasts can enhance renal interstitial scarring and enhance tubular atrophy. 29,31,40 CTGF expression is often marked in stromal myofibroblasts, 12,28 but whether CTGF can induce their transformation from fibroblasts is currently unknown. In addition to differentiation from fibroblasts, transdifferentiation from renal tubular epithelial cells has been described as a mechanism for myofibroblast genesis.…”

Section: Discussionmentioning

confidence: 99%

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Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation

et al. 2000

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Abstract. Connective tissue growth factor (CTGF) has been shown to mediate many actions of transforming growth factor-beta (TGF-␤) in the fibrotic response in several diseases. We compared expression of CTGF, TGF-␤, platelet-derived growth factor (PDGF), TNF-␣, and interleukin-1 (IL-1) by in situ hybridization in Sprague-Dawley rats euthanized at 0, 2, 4, and 8 weeks after 5/6 nephrectomy using the rat remnant kidney model of renal failure. Collagen was evaluated by trichrome stains, immunohistochemistry, and electron microscopy. We compared expression patterns to cells undergoing metaplasia. Tubular epithelial regeneration and transdifferentiation to myofibroblasts were assessed morphologically and by proliferating cell nuclear antigen, smooth muscle actin, desmin, and vimentin immunohistochemistry. CTGF expression was minimal in controls, mild at 2 weeks and marked by 4 to 8 weeks in interstitial fibroblasts, coinciding with damage, regeneration, and fibrosis. TGF-␤ expression was increased in many cell types at 2 weeks, increased further by 4 weeks, then remained constant. PDGF-B messenger RNA was found in many stromal cells at 2-4 weeks, but expression decreased at 8 weeks. No significant IL-1 or TNF-␣ staining was detected. We conclude that CTGF and interacting factors are associated with development or progression of chronic interstitial fibrosis. Proximity of CTGF, TGF-␤, and PDGF mRNA expression to regenerative epithelial cells and those transdifferentiating to myofibroblasts suggests that growth factors may modulate renal tubular epithelial differentiation.

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“…40 CTGF, PDGF and TGF-␤ probably all interact in inducing proliferation of these cells. Both TGF-␤ and PDGF can induce the transformation of fibroblasts into myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation

et al. 2000

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“…[7][8][9] Infiltration by macrophages is invariably observed at sites of renal fibrosis, with the degree of infiltration correlated with the extent of fibrosis. 10,11 Nuclear factor kappa B (NF-κB) is a major signaling pathway that activates and promotes macrophage infiltration.…”

Section: Introductionmentioning

confidence: 99%

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

Morishita¹,

Imai²,

Yoshizawa³

et al. 2015

IJN

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Renal fibrosis is the final common pathway leading to end-stage renal disease. Although microRNA (miR) was recently shown to be involved in the development of renal fibrosis, few studies have focused on the effects on renal fibrosis of exogenous miR delivered in an in vivo therapeutic setting. The study reported here investigated the effects of miR-146a delivery using polyethylenimine nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs bearing miR-146 significantly enhanced miR-146a expression in the obstructed kidney compared with the control group, while inhibiting the renal fibrosis area, expression of alpha-smooth muscle actin, and infiltration of F4/80-positive macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a inhibited the transforming growth factor beta 1–Smad and tumor necrosis factor receptor-associated factor 6–nuclear factor kappa B signaling pathways. Control-miR-PEI-NPs did not show any of these effects. These results suggest that the delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and inflammatory signaling pathways and that the delivery of appropriate miRs may be a therapeutic option for preventing renal fibrosis in vivo.

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“…This view is currently changing because recent studies of human biopsy samples and animal models have established kidney macrophage accumulation as a characteristic of diabetic nephropathy (4 -7). Renal macrophage accumulation correlates with the severity of glomerular and tubulointerstitial injury in experimental diabetic nephropathy (7) and nondiabetic models of renal disease (8,9). Beneficial effects of irradiation (6) and mycophenolate (10) in animal models of diabetic nephropathy have been attributed to inhibition of renal macrophage accumulation.…”

mentioning

confidence: 99%

Intercellular Adhesion Molecule-1 Deficiency Is Protective against Nephropathy in Type 2 Diabetic db/db Mice

Chow¹,

Nikolic-Paterson²,

Ozols³

et al. 2005

Journal of the American Society of Nephrology

248

210

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Diabetic nephropathy is a leading cause of end-stage renal failure and is a growing concern given the increasing incidence of type 2 diabetes. Diabetic nephropathy is associated with progressive kidney macrophage accumulation and experimental studies suggest that intercellular adhesion molecule (ICAM)-1 facilitates kidney macrophage recruitment during type 1 diabetes. To ascertain the importance of ICAM-1 in promoting type 2 diabetic nephropathy, the development of renal injury in ICAM-1 intact and deficient db/db mice with equivalent hyperglycemia and obesity between ages 2 and 8 mo was examined and compared with results with normal db/؉ mice. Increases in albuminuria (11-fold), glomerular leukocytes (10-fold), and interstitial leukocytes (three-fold) consisting of predominantly CD68؉ macrophages were identified at 8 mo in diabetic db/db mice compared with nondiabetic db/؉ mice. In comparison to db/db mice, ICAM-1-deficient db/db mice had marked reductions in albuminuria at 6 mo (77%2) and 8 mo (85%2). There was also a significant decrease in glomerular (63%2) and interstitial (83%2) leukocytes in ICAM-1-deficient db/db mice, which were associated with reduced glomerular hypertrophy and hypercellularity and tubular damage. The development of renal fibrosis (expression of TGF-␤1, collagen IV, and interstitial ␣-smooth muscle actin) was also strikingly attenuated in the ICAM-1-deficient db/db mice. Additional in vitro studies showed that macrophage activation by high glucose or advanced glycation end products could promote ICAM-1 expression on tubular cells and macrophage production of active TGF-␤1. Thus, ICAM-1 appears to be a critical promoter of nephropathy in mouse type 2 diabetes by facilitating kidney macrophage recruitment.

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Local macrophage and myofibroblast proliferation in progressive renal injury in the rat remnant kidney

Cited by 89 publications

References 2 publications

Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation

Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

Intercellular Adhesion Molecule-1 Deficiency Is Protective against Nephropathy in Type 2 Diabetic db/db Mice

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