Mechanisms of tubulointerstitial fibrosis

Kuncio, Gerald S.; Neilson, Eric G.; Haverty, Thomas P.

doi:10.1038/ki.1991.63

Cited by 275 publications

(182 citation statements)

References 52 publications

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“…Furthermore, TGF-β modulates the expression of integrins, which are cell-surface receptors for ECM components, thereby facilitating cell adhesion and matrix deposition [39,40]. TGF-β also acts on (myo)fibroblasts, which are the main source of the increased ECM deposition in tissue fibrosis: TGF-β is a chemoattractant for fibroblasts [41], stimulates fibroblast proliferation [42], and regulates transdifferentiation of resident kidney cells into myofibroblasts [43].…”

Section: Transforming Growth Factor-betamentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

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Section: Transforming Growth Factor-betamentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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“…This may partially be attributed to the fact that it was long considered the exclusive domain of descriptive ultrastructural research, which implied that the interstitium was mostly a passive tissue that structurally supported the tubular epithelium (1,2). The renal interstitium received increasing interest in the context of kidney abnormalities, when the role of interstitial fibrosis in progression of CKD became obvious (3)(4)(5). Only since transgenic animal studies revealed the physiologic endocrine function of interstitial cells as sources of erythropoietin (Epo) and renin has the physiologic role of the renal interstitium received its due attention.…”

Section: Introductionmentioning

confidence: 99%

Physiology of the Renal Interstitium

Zeisberg

Kalluri

2015

Clinical Journal of the American Society of Nephrology

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Long overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial reninand erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.

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“…Renal interstitial fibrosis develops following renal tubular and glomerular injury (4,19,31,35,37,45). The fibrotic lesion is evoked through complex pathologic processes, requiring participation of various inflammatory cells and abnormal accumulation of extracellular matrices (ECM) (5,7,9,19,35,39).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Analysis of Macrophages, Myofibroblasts, and Transforming Growth Factor-β Localization during Rat Renal Interstitial Fibrosis Following Long-Term Unilateral Ureteral Obstruction

et al. 1998

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Renal interstitial fibrosis was induced in rats by chronic unilateral ureteral obstruction (UUO). To identify the mechanisms behind the fibrosis, macrophage influx, myofibroblast involvement, and the localization of transforming growth factor-β (TGF-β, a fibrogenic cytokine) were investigated immunohistochemically in rats euthanatized at 0 (controls), 3,6,9,12, and 15 days after UUO. The number of α-smooth muscle actin-positive myofibroblasts began to increase significantly in the medulla from day 3, and the development of medullary fibrosis was confirmed from day 6 by morphometric analysis. From day 9, papillary fibrosis also developed in association with an increased number of myofibroblasts. These myofibroblasts showed a parallel orientation to the mucosal surface of the pelvis. In the medulla and papilla, from day 6 the number of ED1 (primary antibody)-positive macrophages began to increase significantly. There appeared to be a relationship between macrophage influx and myofibroblast involvement. By contrast, in the cortex there was no marked increase in myofibroblasts nor development of fibrotic tissues, regardless of increased number of macrophages from day 6. Immunohistochemically, no staining for TGF-β was found in infiltrating macrophages or myofibroblasts. However, TGF-& b e t a ; was localized on some cortical proximal renal tubules both of normal control and obstructed kidneys in the early stages on days 3, 6, and 9, suggesting that the possible origin of TGF-β may be renal epithelia. However, the staining intensity for TGF-β on the renal epithelia tended to be weakened in advanced obstructed kidneys on days 12 and 15. The likely contribution of TGF-β to the advanced stages of UUO-induced renal fibrosis remains to be determined.

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Mechanisms of tubulointerstitial fibrosis

Cited by 275 publications

References 52 publications

ECM homeostasis in renal diseases: a genomic approach

ECM homeostasis in renal diseases: a genomic approach

Physiology of the Renal Interstitium

Immunohistochemical Analysis of Macrophages, Myofibroblasts, and Transforming Growth Factor-β Localization during Rat Renal Interstitial Fibrosis Following Long-Term Unilateral Ureteral Obstruction

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