TGF-β/BMP proteins as therapeutic targets in renal fibrosis. Where have we arrived after 25years of trials and tribulations?

Muñoz‐Félix, José M.; González-Núñez, María; Martı́nez-Salgado, Carlos; López‐Novoa, José M.

doi:10.1016/j.pharmthera.2015.10.003

Cited by 72 publications

(55 citation statements)

References 208 publications

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“…3). Some BMPs (such as BMP1 or BMP3) induce kidney fibrosis by binding to TGF-β superfamily type II receptors, whereas others (such as BMP7) prevent fibrosis 147,148 . The effects of BMP on these receptors…”

Section: Fgf-23 Bridges Multiple Organs and Systemsmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

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Section: Fgf-23 Bridges Multiple Organs and Systemsmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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“…There are a number of pro-fibrotic pathways in the kidney that have been identified; perhaps transforming growth factor-beta 1 (TGF-1) is the most well-studied pathway in renal fibrosis (Meng et al, 2015;Munoz-Felix et al, 2015). Much work has focused on the ability of TGF-1 to induce EMT and SMA expression (Iwano, 2010).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The cytoskeleton as a novel target for treatment of renal fibrosis

Parrish

2016

Pharmacology & Therapeutics

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“…A hallmark of DN as it progresses towards end-stage renal disease is renal fibrosis, which is accompanied by irreversible loss of renal function 20 . Past research showed that reducing renal fibrosis by decreasing the synthesis of extracellular matrix (ECM) protein, such as fibronectin and collagen IV, could delay the development of DN 20 .…”

Section: R E T R a C T E Dmentioning

confidence: 99%

“…Effects of UII on ECM protein synthesis of kidney tissues in diabetic mice ECM proteins (fibronectin and collagen IV) are known to accumulate in early DN 20 . To gain insights into the effects of UII and autophagy on ECM proteins production in diabetes, we carried out immunochemical staining of renal tissues from the diabetic UT knockout mice, diabetic wild-type mice and normal …”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

Chen

Pang

et al. 2016

J of Diabetes Invest

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Aims/Introduction: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. Materials and Methods: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10 -7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10 -6 mol/L) or autophagy inducer, rapamycin (10 -3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/ SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. Results: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV.Conclusions: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.

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TGF-β/BMP proteins as therapeutic targets in renal fibrosis. Where have we arrived after 25years of trials and tribulations?

Cited by 72 publications

References 208 publications

The systemic nature of CKD

The systemic nature of CKD

The cytoskeleton as a novel target for treatment of renal fibrosis

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

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