Activation of the TGF- β/Smad signaling pathway in focal segmental glomerulosclerosis

Kim, Ji Hoon; Kim, Byoung Kwon; Moon, Kyung Chul; Hong, Hye Kyoung; Lee, Hyun Soon

doi:10.1046/j.1523-1755.2003.00288.x

Cited by 128 publications

(105 citation statements)

References 51 publications

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“…In patients with focal segmental glomerulosclerosis (FSGS), fresolimumab treatment was associated with a decline in proteinuria in some patients, suggesting possible efficacy in this disease, for which TGF-β is also strongly implicated in pathogenesis (41,42). Like in SSc, THBS1 is overexpressed in FSGS renal glomeruli (43,44), suggesting that it may provide a strong biomarker in other TGF-β-mediated diseases.…”

Section: Discussionmentioning

confidence: 99%

Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Rice¹,

Padilla²,

McLaughlin³

et al. 2015

J. Clin. Invest.

282

208

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Section: Discussionmentioning

confidence: 99%

Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Rice¹,

Padilla²,

McLaughlin³

et al. 2015

J. Clin. Invest.

282

208

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“…As a key regulator of extracellular matrix, TGF-␤ has been implicated as an important mediator of renal fibrosis (22,23), particularly in FSGS (24). Pirfenidone not only suppresses TGF-␤ gene expression at the transcriptional level but also inhibits protein expression of TGF-␤ by 80% (25,26).…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Slows Renal Function Decline in Patients with Focal Segmental Glomerulosclerosis

Cho¹,

Smith²,

Branton³

et al. 2007

Clinical Journal of the American Society of Nephrology

184

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Background and Objectives: Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glomerulosclerosis.Design, Setting, Participants, & Measurements: An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in estimated GFR, expressed as ml/min per 1.73 m 2 , was compared between the baseline period and the treatment period. During both periods, patients received angiotensin antagonist therapy if tolerated. Twenty-one patients were enrolled, and 18 patients completed a median of 13 mo of pirfenidone treatment.Results: The monthly change in GFR improved from a median of ؊0.61 ml/min per 1.73 m 2 (interquartile range ؊1.31 to ؊0.41) during the baseline period to ؊0.45 ml/min per 1.73 m 2 (interquartile range ؊0.78 to ؊0.16) with pirfenidone therapy. This change represents a median of 25% improvement in the rate of decline (P < 0.01). Pirfenidone had no effect on BP or proteinuria. Adverse events attributed to therapy included dyspepsia, sedation, and photosensitive dermatitis.Conclusions: It is concluded that pirfenidone is an attractive candidate for placebo-controlled trials in patients with progressive chronic kidney disease.

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“…EMT, among other mechanisms, to form the glomerular scar [83,84]. Recent data demonstrate that WT1 is down-regulated by TGFβ1 in both cultured podocytes and transgenic mice overexpressing TGFβ1, prior to podocyte loss [85].…”

Section: Developmental Renal Diseasementioning

confidence: 99%

WT1 in disease: shifting the epithelial–mesenchymal balance

Miller-Hodges

Hohenstein

2011

The Journal of Pathology

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WT1 is a versatile gene that controls transitions between the mesenchymal and epithelial state of cells in a tissue-context dependent manner. As such, WT1 is indispensable for normal development of many organs and tissues. Uncontrolled epithelial to mesenchymal transition (EMT) is a hallmark of a diverse array of pathologies and disturbance of mesenchymal to epithelial transition (MET) has been associated with a number of developmental abnormalities. It is therefore not surprising that WT1 has been linked to many of these. Here we review the role of WT1 in proper control of the mesenchymal-epithelial balance of cells and discuss how far these roles can explain the role of WT1 in a variety of disease states.

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Activation of the TGF- β/Smad signaling pathway in focal segmental glomerulosclerosis

Cited by 128 publications

References 51 publications

Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Pirfenidone Slows Renal Function Decline in Patients with Focal Segmental Glomerulosclerosis

WT1 in disease: shifting the epithelial–mesenchymal balance

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