Increased Activity of Activator Protein-1 Transcription Factor Components ATF2, c-Jun, and c-Fos in Human and Mouse Autosomal Dominant Polycystic Kidney Disease

Le, Ngoc Hang; Wal, Annemieke van der; Bent, Paola van der; Leeuwen, Irma S. Lantinga-van; Breuning, Martijn H.; Dam, Hans van; Heer, Emile de; Peters, Dorien J.M.

doi:10.1681/asn.2004110913

Cited by 50 publications

(24 citation statements)

References 33 publications

(25 reference statements)

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“…The core “TGAC” sequence recognized by Jun/ATF2 heterodimer is, in fact, identical in AP1 and CREB consensus sites [30]; it is present in AR-pGL2C and AR-pGL2C-ΔCRE but not in the AR-pGL2C-mut construct. This observation suggests a new mechanism for the altered activities of c-Jun and ATF2 in the renal cystic tissue of ADPKD patients [31, 32]. …”

Section: Discussionmentioning

confidence: 99%

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation

et al. 2012

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In autosomal dominant polycystic kidney disease (ADPKD), renal cyst development and enlargement, as well as cell growth, are associated with alterations in several pathways, including cAMP and activator protein 1 (AP1) signalling. However, the precise mechanism by which these molecules stimulate cell proliferation is not yet fully understood. We now show by microarray analysis, luciferase assay, mutagenesis, and chromatin immunoprecipitation that CREB and AP1 contribute to increased expression of the amphiregulin gene, which codifies for an epidermal growth factor-like peptide, in ADPKD cystic cells, thereby promoting their cell growth. Increased amphiregulin (AR) expression was associated with abnormal cell proliferation in both PKD1-depleted and -mutated epithelial cells, as well as primary cystic cell lines isolated from ADPKD kidney tissues. Consistently, normal AR expression and proliferation were re-established in cystic cells by the expression of a mouse full-length PC1. Finally, we show that anti-AR antibodies and inhibitors of AP1 are able to reduce cell proliferation in cystic cells by reducing AR expression and EGFR activity. AR can therefore be considered as one of the key activators of the growth of human ADPKD cystic cells and thus a new potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation

et al. 2012

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“…Altered TLR4 signaling may also affect the AP-1 signaling pathway (reviewed in Hu et al 39 ) that has been linked to cystogenesis in PKD1 defects. 40 Since TLR4 is expressed across the nephron including proximal tubules and collecting ducts (summarized in Good et al 41 ), it is possible that renal tubular cell-derived CD14 may activate TLR4 locally in a paracrine (perhaps even autocrine) fashion. Alternatively, filtered or exosomal CD14 42 (that may be in part proximal nephron-derived) may exert more distal effects, e.g., by activating TLR4 on principal cells of collecting duct, a major cyst-forming cell type.…”

Section: Discussionmentioning

confidence: 99%

Renal CD14 expression correlates with the progression of cystic kidney disease

Zhou

Ouyang

Cui

et al. 2010

Kidney International

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Monocyte and macrophage markers are among the most highly overexpressed genes in cpk mouse kidneys with severely progressive renal cystic disease. We now demonstrate that one of these markers, CD14, is abnormally transcribed, activated and shed in cystic kidneys. However, these abnormalities are not associated with an increased number of interstitial CD14-positive mononuclear cells. Instead, we show that most non-cystic and cystic renal tubular epithelia are CD14-positive and that CD14 can be produced even by distal nephron-derived principal cells. Cd14 overexpression is significant in as early as 5-d old sporadically cystic cpk kidneys and it further increases during the disease progression. Similarly, in a cpk model with variable rates of cystic kidney disease progression, a (C57BL/6J-cpk × CAST/Ei)F1 intercross, Cd14 expression positively correlates with kidney volume in 10-d old mice, exceeding the correlation of a gene encoding an established autosomal dominant polycystic kidney disease (ADPKD) marker, MCP-1 (r=0.94 vs. r=0.79; both p<0.001). Similarly, in a small group of ADPKD patients (n=16), baseline urinary CD14 levels (but not GFR) correlate with a two-year rate of total kidney volume change (overall r=0.43, p=0.09; for males r=0.74, p=0.02) suggesting potential utility of CD14 in predicting ADPKD outcomes.

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“…However, overexpression of c-Fos may lead to some diseases, such as cardiac ischemia-reperfusion, myocardial stunning, and heart failure (Corbucci, 2000;Itoh et al, 2000;Patel et al, 2000;Nelson et al, 2002;Le et al, 2005;Turatti et al, 2005;Wang et al, 2005;Sakai et al, 2007;Aikawa et al, 2008). As an example, the expression of Fos protein presents an apparent increase in rat models of myocardial stunning.…”

Section: Monoclonal Antibody Therapy Against Apoptosismentioning

confidence: 99%

Advances in monoclonal antibody application in myocarditis

Han

Wang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Monoclonal antibodies have become a part of daily preparation technologies in many laboratories. Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases, inflammatory diseases, cancer, and other immune-associated diseases. This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis, an inflammatory disease of the heart, could be a novel approach in the future. In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis, we, through a significant amount of literature research both domestic and abroad, developed a systematic elaboration of monoclonal antibodies, pathogenesis of myocarditis, and application of monoclonal antibodies in myocarditis. This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future. Under conventional therapy, myocarditis is typically associated with congestive heart failure as a progressive outcome, indicating the need for alternative therapeutic strategies to improve long-term results. Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis, we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above. However, several issues remain. The technology on how to make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues. If we are to further stimulate progress in the area of clinical decision support, we must continue to develop and refine our understanding and use of monoclonal antibodies in myocarditis.

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Increased Activity of Activator Protein-1 Transcription Factor Components ATF2, c-Jun, and c-Fos in Human and Mouse Autosomal Dominant Polycystic Kidney Disease

Cited by 50 publications

References 33 publications

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation

Renal CD14 expression correlates with the progression of cystic kidney disease

Advances in monoclonal antibody application in myocarditis

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