The TGF-β co-receptor endoglin regulates macrophage infiltration and cytokine production in the irradiated mouse kidney

Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Stewart, Fiona

doi:10.1016/j.radonc.2012.08.021

Cited by 37 publications

(33 citation statements)

References 57 publications

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“…The expression of these adhesion molecules was lower in the obstructed kidney of S-ENG + compared with that from WT mice, although the difference was not significant. The involvement of Eng in inflammatory cell infiltration in experimental models of kidney damage has been already demonstrated [33,37]. Thus, all our data suggest a lower inflammatory status in the O kidneys from S-ENG + mice compared with…”

Section: Accepted Manuscriptsupporting

confidence: 79%

“…In agreement with these reports, our present data in the UUO model of tubulo-interstitial fibrosis shows the increase in both Eng mRNA and protein expression in the O kidney ( Figure 1). Several authors demonstrated that Eng promotes fibrosis in different kidney experimental models [15,16,[33][34][35][36][37] and other experimental models of tissue fibrosis in organs such as heart [13,38], liver [39] or skin [40]. Two different Eng isoforms that differs exclusively in the intracellular tail have been reported in both humans [18] and mice [19].…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Muñoz‐Félix

Pérez-Roque

Núñez-Gómez

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Transforming growth factor beta 1 (TGF-β1) is one of the most studied cytokines involved in renal tubulo-interstitial fibrosis, which is characterized by myofibroblast abundance and proliferation, and high buildup of extracellular matrix in the tubular interstitium leading to organ failure. Endoglin (Eng) is a 180-kDa homodimeric transmembrane protein that regulates a great number of TGF-β1 actions in different biological processes, including ECM synthesis. High levels of Eng have been observed in experimental models of renal fibrosis or in biopsies from patients with chronic kidney disease. In humans and mice, two Eng isoforms are generated by alternative splicing, L-Eng and S-Eng that differ in the length and composition of their cytoplasmic domains. We have previously described that L-Eng overexpression promotes renal fibrosis after unilateral ureteral obstruction (UUO). However, the role of S-Eng in renal fibrosis is unknown and its study would let us analyze the possible function of the cytoplasmic domain of Eng in this process. For this purpose, we have generated a mice strain that overexpresses S-Eng (S-ENG(+)) and we have performed an UUO in S-ENG(+) and their wild type (WT) control mice. Our results indicate that obstructed kidney of S-ENG(+) mice shows lower levels of tubulo-interstitial fibrosis, less inflammation and less interstitial cell proliferation than WT littermates. Moreover, S-ENG(+) mice show less activation of Smad1 and Smad2/3 pathways. Thus, S-Eng overexpression reduces UUO-induced renal fibrosis and some associated mechanisms. As L-Eng overexpression provokes renal fibrosis we conclude that Eng-mediated induction of renal fibrosis in this model is dependent on its cytoplasmic domain.

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Section: Accepted Manuscriptsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Muñoz‐Félix

Pérez-Roque

Núñez-Gómez

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Eng is present in monocytes, and it is up-regulated during the monocyte-macrophage transition and in endothelial cells of inflamed tissues [50], [51]. Recent works support the role of Eng in leukocyte adhesion, transmigration and interleukin production [52], [53]. In opposite way, sEng has the ability to inhibit leukocyte adhesion [52].…”

Section: Discussionmentioning

confidence: 99%

Soluble Endoglin, Transforming Growth Factor-Beta 1 and Soluble Tumor Necrosis Factor Alpha Receptors in Different Clinical Manifestations of Preeclampsia

Perucci¹,

Gomes

Freitas³

et al. 2014

PLoS ONE

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BackgroundDespite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE.MethodsPlasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)].ResultsPregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity.ConclusionsThese results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation.

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Section: Introductionmentioning

confidence: 99%

“…The underlying pathogenesis of radiation-induced nephrotoxicity has been a topic of extensive research. Inflammatory events associated with microvascular damage have been recognized as important contributing factors [10][11][12][13].In radiotherapy treatment planning, baseline function and anatomic location of both kidneys should be considered because both contribute to overall renal function and one can compensate reduced function of the other. The compensatory response is optimal when one kidney receives less than 18 Gy to at least two-thirds of its total volume [14].…”

mentioning

confidence: 99%

IMRT limits nephrotoxicity after chemoradiotherapy for gastric cancer

Trip

Nijkamp

Tinteren

et al. 2014

Radiotherapy and Oncology

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The TGF-β co-receptor endoglin regulates macrophage infiltration and cytokine production in the irradiated mouse kidney

Cited by 37 publications

References 57 publications

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Soluble Endoglin, Transforming Growth Factor-Beta 1 and Soluble Tumor Necrosis Factor Alpha Receptors in Different Clinical Manifestations of Preeclampsia

IMRT limits nephrotoxicity after chemoradiotherapy for gastric cancer

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