Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model

Cañadillas, Sagrario; Ortega, Rosa; Estepa, J. C.; Egea, Jeronimo; González-Menchen, Alberto; Pérez-Seoane, C; Lopez-Andreu, M.; Ramı́rez, Rafael; Tetta, Ciro; Rodriguez, Mariano; Martín‐Malo, Alejandro; Aljama, Pedro

doi:10.1152/ajprenal.00343.2009

Cited by 11 publications

(15 citation statements)

References 24 publications

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“…Double staining was also performed for KIM-1 and the PEC protein claudin-1 [5], as well as KIM-1 and the podocyte injury marker desmin [17]. As shown in figure 4a, cells positive for both KIM-1 and claudin-1 were detected along the parietal layer of Bowman’s capsule in the Fa/Fa animals.…”

Section: Resultsmentioning

confidence: 99%

Glomerular Expression of Kidney Injury Molecule-1 and Podocytopenia in Diabetic Glomerulopathy

Zhao

Zhang

et al. 2011

Am J Nephrol

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Background/Aims: Studies have shown that kidney injury molecule-1 (KIM-1) is upregulated in damaged renal proximal tubules. In this study, we examined KIM-1 expression in glomerular epithelial cells in diabetic glomerulopathy. Methods: Renal histology, immunostaining and Western blot for protein level, and real-time PCR for mRNA expression of KIM-1 and podocyte markers were evaluated in untreated or losartan-treated Zucker lean (Fa/+) and Zucker diabetic fatty (Fa/Fa) rats. Results: The diabetic rats showed an increased glomerular expression of KIM-1. KIM-1 staining was localized primarily in the hyperplastic parietal epithelium of Bowman’s capsule in the early stages of diabetes with subsequent increase in KIM-1-positive cells in the glomerular tuft in the more advanced stages. The increase in glomerular KIM-1 was associated with a decrease in podocytes in Fa/Fa rats. Antiproteinuric treatment with losartan attenuated podocytopenia and decreased renal expression of KIM-1 in treated diabetic rats. In an in vitro study, albumin overload increased KIM-1 protein in the primary cultures of rat glomerular epithelial cells. Conclusion: These results show that glomerular KIM-1 expression was increased, in proportion to the extent of proteinuria and podocytopenia in the diabetic animals, supporting that KIM-1 could be used as a potential biomarker for glomerular injury in proteinuric kidney disease.

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Section: Resultsmentioning

confidence: 99%

Glomerular Expression of Kidney Injury Molecule-1 and Podocytopenia in Diabetic Glomerulopathy

Zhao

Zhang

et al. 2011

Am J Nephrol

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“…EPO also can provide protection for renal cells during toxic insults [41,42]. In the liver, EPO has been shown to protect against ischemic-reperfusion injury [43], but excessive over-expression of EPO can lessen the beneficial effects of EPO [44].…”

Section: Epo Structure and Expressionmentioning

confidence: 99%

Erythropoietin: New Directions for the Nervous System

Maiese

Chong

Shang

et al. 2012

IJMS

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New treatment strategies with erythropoietin (EPO) offer exciting opportunities to prevent the onset and progression of neurodegenerative disorders that currently lack effective therapy and can progress to devastating disability in patients. EPO and its receptor are present in multiple systems of the body and can impact disease progression in the nervous, vascular, and immune systems that ultimately affect disorders such as Alzheimer’s disease, Parkinson’s disease, retinal injury, stroke, and demyelinating disease. EPO relies upon wingless signaling with Wnt1 and an intimate relationship with the pathways of phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Modulation of these pathways by EPO can govern the apoptotic cascade to control β-catenin, glycogen synthase kinase-3β, mitochondrial permeability, cytochrome c release, and caspase activation. Yet, EPO and each of these downstream pathways require precise biological modulation to avert complications associated with the vascular system, tumorigenesis, and progression of nervous system disorders. Further understanding of the intimate and complex relationship of EPO and the signaling pathways of Wnt, PI 3-K, Akt, and mTOR are critical for the effective clinical translation of these cell pathways into robust treatments for neurodegenerative disorders.

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“…Darbepoetin has been shown to reduce proteinuria and facilitates glomerular repair in Thy-1 rat glomerulonephritis model, 84 proteinuria in rat PAN, 85 and proteinuria and podocyte apoptosis in antiglomerular serum-induced mouse glomerulonephritis. 86 In the latter study, the effects were attributed to activation by darbepoetin of the AKT cell survival pathway.…”

Section: Overview Of Non-renin–angiotensin–aldosterone System Agentsmentioning

confidence: 99%

Off the Beaten Renin–Angiotensin–Aldosterone System Pathway: New Perspectives on Antiproteinuric Therapy

Gordon

Kopp²

2011

Advances in Chronic Kidney Disease

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CKD is a major public health problem in the developed and the developing world. The degree of proteinuria associated with renal failure is a generally well accepted marker of disease severity. Agents with direct antiproteinuric effects are highly desirable therapeutic strategies for slowing, or even halting, progressive loss of kidney function. We review progress on therapies acting further downstream of the renin–angiotensin–aldosterone system pathway (e.g., transforming growth factor-beta antagonism, endothelin antagonism) and on those acting independent of the renin–angiotensin–aldosterone system pathway. In all, we discuss 26 therapeutic targets or compounds and 2 lifestyle changes (dietary modification and weight loss) that have been used clinically for diabetic or nondiabetic kidney disease. These therapies include endogenous molecules (estrogens, isotretinoin), biologic antagonists (monoclonal antibodies, soluble receptors), and small molecules. Where mechanistic data are available, these therapies have been shown to exert favorable effects on glomerular cell phenotype. In some cases, recent work has indicated surprising new molecular pathways for some therapies, such as direct effects on the podocyte by glucocorticoids, rituximab, and erythropoietin. It is hoped that recent advances in the basic science of kidney injury will prompt development of more effective pharmaceutical and biologic therapies for proteinuria.

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Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model

Cited by 11 publications

References 24 publications

Glomerular Expression of Kidney Injury Molecule-1 and Podocytopenia in Diabetic Glomerulopathy

Glomerular Expression of Kidney Injury Molecule-1 and Podocytopenia in Diabetic Glomerulopathy

Erythropoietin: New Directions for the Nervous System

Off the Beaten Renin–Angiotensin–Aldosterone System Pathway: New Perspectives on Antiproteinuric Therapy

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