Localization of TGF-β and Its Receptors in the Kidney

Ando, Takashi; Okuda, Seiya; Yanagida, Taihei; Fujishima, Masatoshi

doi:10.1159/000057363

Cited by 28 publications

(15 citation statements)

References 28 publications

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“…Numerous members of the TGF-β superfamily have been localized and shown to exert functions within the kidney (Ritvos et al 1995;Pichel et al 1996;Ando et al 1998). Figure 6 reveals that strong signals specific for GDF-15/MIC-1 mRNA can be localized to the S3 segments, while lower levels of GDF-15/MIC-1 mRNA can be detected in collecting ducts.…”

Section: Resultsmentioning

confidence: 99%

Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

Böttner

Suter‐Crazzolara

Schober

et al. 1999

Cell and Tissue Research

157

122

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We have cloned a novel member of the transforming growth factor-beta (TGF-beta) superfamily from a human placental cDNA library. The sequence is identical to five very recently published sequences, of which only one (macrophage inhibitory cytokine-1, MIC-1) has been characterized in terms of function. In light of the present data demonstrating the wide distribution of the mRNA and putative multifunctionality, we propose to name this molecule growth/differentiation factor-15/MIC-1 (GDF-15/MIC-1). The deduced amino acid sequence reveals typical features of a secreted molecule. The epithelium of the choroid plexus is the only site in the adult brain expressing detectable levels of GDF-15/MIC-1 mRNA. Many epithelia of non-neural tissues including those of the prostate and intestinal mucosa, bronchi and bronchioli, secretory tubuli of the submandibular gland, and lactating mammary gland are prominent sites of GDF-15/MIC-1 synthesis. GDF-15/MIC-1 is also strongly expressed by macrophages in the adrenal gland. Thus, GDF-15/MIC-1, like many other members of the TGF-beta superfamily, is widely distributed in adult tissues, being most strongly expressed in epithelial cells and macrophages.

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Section: Resultsmentioning

confidence: 99%

Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

Böttner

Suter‐Crazzolara

Schober

et al. 1999

Cell and Tissue Research

157

122

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“…The TGF-β superfamily includes three isoforms: TGF-βl, -β2 and -β3, each encoded by a distinct gene, and all expressed in the kidney [6]. Among these, TGF-βl is most abundantly produced by mammalian cells.…”

Section: Renal Tgf-β Expression and Signallingmentioning

confidence: 99%

Therapeutic potential of TGF-β inhibition in chronic renal failure

Gagliardini¹,

Benigni²

2007

Expert Opinion on Biological Therapy

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Chronic kidney diseases are emerging as a worldwide public health problem. The progression of kidney diseases closely correlates with the accumulation of extracellular matrix leading to glomerulosclerosis and tubulointerstitial injury. Transforming growth factor (TGF)-beta has been identified as a key mediator of kidney matrix accumulation. Overexpression of TGF-beta isoforms and their receptors was observed in a variety of renal diseases in both animals and humans. Given its crucial role in fibrotic kidney disease, TGF-beta has been recently considered as a possible target in the management of chronic renal diseases. This review discusses the role of TGF-beta in renal fibrosis and provides an overview of the strategies that, when interfering with TGF-beta expression and signalling, could be employed as new renoprotective treatments.

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“…In addition to its role which directly links the activity of the AS to the activity of the local RAS. Thus in a model of IDDM, the epithelial in embryogenesis [109] and kidney development [91,110], TGF-is also thought to play a role in renal tissue remodcells of the S1 proximal tubules may rapidly process angiotensinogen by an intracellular mechanism which is elling in various disorders including diabetes [111,112].…”

Section: Amylin and Diabetesmentioning

confidence: 99%

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

Wookey

Cao²,

Cooper

1998

Mineral Electrolyte Metab

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The range of known actions of amylin are reviewed together with the proposal that an important role for amylin may be the hormonal integration of diverse physiological systems activated with feeding. Major targets for the action of amylin are found within the kidney. Components of the amylin system (AS) have been shown to influence the activity of components of the renin-angiotensin system (RAS), and vice versa, in normal, hypertensive and diabetic models. For instance, amylin injected into humans and rats elicits a rapid rise in plasma renin activity. Furthermore, in two models of hypertension (the spontaneously hypertensive rat (SHR) and the model with subtotal nephrectomy (STNx)), the density of amylin-binding sites in the renal cortex associated with the proximal tubules, was associated with elevation of blood pressure. In normotensive controls and in the STNx model, but not in the SHR model, treatment with angiotensin-converting enzyme (ACE) inhibitors reduced blood pressure and the density of amylin binding in the renal cortex. In Sprague-Dawley rats, angiotensin II (Ang II) infusion was associated with increased density of amylin-binding sites as well as elevated blood pressure. Thus, there appears to be a direct relationship between the activity of Ang II and the binding sites for amylin in the renal cortex. From these studies it has been postulated that the activation of the AS in the kidney may play a role in the genesis and/or development of hypertension in certain contexts. The transient expression of amylin mRNA has been detected perinatally, using in situ hybridization, in the subnephrogenic zone of the metanephros and is associated with proximal tubules of the developing nephron. These cells situated close to the glomeruli, represent a subset of brush border epithelial cells. Amylin immunoreactivity (IR) is also found in these cells and colocalizes with angiotensinogen IR. Thus a second important role for amylin is described in which it plays a role as a growth factor in the developing kidney and in renal regrowth in the adult kidney. In a model of IDDM (streptozotocin diabetes), amylin and angiotensinogen IR are both restricted to a subset of brush border epithelial cells close to glomeruli which, in the developing kidney, expressed amylin mRNA. Thus in this IDDM model, we hypothesize that amylin mRNA transcription which is normally downregulated in the adult, is upregulated in this subset of these brush border epithelial cells, and that it stimulates the activity of a local RAS by an intracellular mechanism, leading to the biosynthesis of Ang II. It remains to be determined that if amylin is playing a role in stimulating local Ang II production at these sites, this provides a mechanism for activation of TGF-β, ultimately leading to interstitial fibrosis.

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Localization of TGF-β and Its Receptors in the Kidney

Cited by 28 publications

References 28 publications

Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

Therapeutic potential of TGF-β inhibition in chronic renal failure

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

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