Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat

Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismaı̈l; Tanguay, Jean‐François; Calderone, Angelino

doi:10.1152/ajpheart.00804.2014

Cited by 16 publications

(37 citation statements)

References 44 publications

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“…[14] Prior to surgery, rats received a subcutaneous injection of buprenorphine (0.05 mg/kg; 6–8 hours prior to surgery) and subsequently anesthetized with 5% isoflurane and reduced to 1,5% during the surgical procedure. Following surgery, rats received two injections of buprenorphine at 6 hour intervals and a single dose of ketoprofen (5 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…Two weeks following surgery, sham and banded rats were anesthetized with ketamine/xylazine (100/10 mg/kg) and mean arterial pressure and left ventricular function were determined with a Millar catheter, as previously described. [14] Following hemodynamic measurements, the heart was excised, the atria and ventricles weighed, immersed in liquid nitrogen and stored at -80°C. In a subpopulation of normal and suprarenal abdominal aorta constricted rats, the heart was excised and immediately fixed in formalin.…”

Section: Methodsmentioning

confidence: 99%

“…Formalin-fixed tissue sections of 5–10 μm in thickness were stained with haematoxylin-phloxin-saffron (HPS) and Masson's trichrome to assess cardiac morphology and fibrosis respectively, as previously described. [14] Images were captured with the Olympus QICAM colour video camera interfaced with an Olympus CKX41 microscope and the program Image-Pro calculated collagen content and the data normalized to the area.…”

Section: Methodsmentioning

confidence: 99%

“…[13] Biologically, several distinct functions were attributed to nestin including cellular proliferation, migration and a pro-survival anti-apoptotic phenotype. [6,7,14–17] Collectively, these observations provided the impetus to test the hypothesis that nestin protein levels were upregulated in the hypertrophied/fibrotic left ventricle following suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats and induction of the intermediate filament protein in ventricular fibroblasts by putative pro-fibrotic peptide growth factors may represent a phenotypic marker of an activated state during reactive fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells

et al. 2017

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Renal and lung fibrosis was characterized by the accumulation of collagen-immunoreactive mesenchymal cells expressing the intermediate filament protein nestin. The present study tested the hypothesis that nestin expression was increased in the hypertrophied/fibrotic left ventricle of suprarenal abdominal aorta constricted adult male Sprague-Dawley rats and induced in ventricular fibroblasts by pro-fibrotic peptide growth factors. Nestin protein levels were upregulated in the pressure-overloaded left ventricle and expression positively correlated with the rise of mean arterial pressure. In sham and pressure-overloaded hearts, nestin immunoreactivity was detected in collagen type I(+)-and CD31(+)-cells identified in the interstitium and perivascular region whereas staining was absent in smooth muscle α-actin(+)-cells. A significantly greater number of collagen type I(+)-cells co-expressing nestin was identified in the left ventricle of pressure-overloaded rats. Moreover, an accumulation of nestin(+)-cells lacking collagen, CD31 and smooth muscle α-actin staining was selectively observed at the adventitial region of predominantly large calibre blood vessels in the hypertrophied/fibrotic left ventricle. Angiotensin II and TGF-β1 stimulation of ventricular fibroblasts increased nestin protein levels via phosphatidylinositol 3-kinase- and protein kinase C/SMAD3-dependent pathways, respectively. CD31/eNOS(+)-rat cardiac microvascular endothelial cells synthesized/secreted collagen type I, expressed prolyl 4-hydroxylase and TGF-β1 induced nestin expression. The selective accumulation of adventitial nestin(+)-cells highlighted a novel feature of large vessel remodelling in the pressure-overloaded heart and increased appearance of collagen type I/nestin(+)-cells may reflect an activated phenotype of ventricular fibroblasts. CD31/collagen/nestin(+)-interstitial cells could represent displaced endothelial cells displaying an unmasked mesenchymal phenotype, albeit contribution to the reactive fibrotic response of the pressure-overloaded heart remains unknown.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells

et al. 2017

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“…Nestin, a cytoskeleton protein, is stably expressed in podocytes [7]. Nestin expression was also detected in normal and pre-eclamptic placental tissues and in endothelial cells of the chorionic villi [8].…”

Section: Introductionmentioning

confidence: 99%

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Yang¹,

Ding²,

Yang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that is characterised by a high incidence of hypertension and proteinuria. Podocytes are involved in the formation of a split membrane, which is the last barrier preventing the leakage of protein into the urine. Nestin, a cytoskeleton protein, is expressed stably in podocytes. However, the association between the Nestin concentration in urine and the progression of PE and the role of Nestin in PE remains unclear. Methods: In the present study, a mouse podocyte cell line, PE-like animal model and PE patients’ urine samples were used. Eilsa kits were used to detect the levels of proteins expression in urine samples from patients and animal models. Western Blotting and immunofluorescence were used to detect proteins expression levels in cell samples and animal tissue samples. Flow cytometry was used to detect the level of apoptosis in cells. Tunel assay was used to detect the levels of apoptosis in animal tissue samples. Results: Nestin levels were significantly increased in PE patients than in hypertensive patients and healthy subjects, and positively correlated with proteinuria and podocalyxin. Ang II treatment decreased the expression of Nestin and Podocin in a time- and dose- dependent manner in podocytes. Restoration of the Nestin levels could reverse Ang II-induced F-actin degradation and attenuate Ang II-mediated podocyte apoptosis, while knockdown of the Nestin level exhibited the opposite. Moreover, the protective role of Nestin on podocytes is mediated by inhibition of the kinase activity of CDK5. In PE-like animal model induced by L-NAME injection, restoration of Nestin lowered the pressure and proteinuria concentration, attenuated the loss of podocytes, and decreased the expression of p35, p53 and the activity of CDK5 kinase, as compared with the control. Conclusions: Our findings suggest that Nestin could improve preeclampsia-like symptoms by inhibiting the activity of CDK5, and Nestin may become a new prognostic factor and a potential therapy target for PE.

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Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression

et al. 2015

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Endothelial and epithelial cell transition to a mesenchymal phenotype was identified as cellular paradigms implicated in the appearance of fibroblasts and development of reactive fibrosis in interstitial lung disease. The intermediate filament protein nestin was highly expressed in fibrotic tissue, detected in fibroblasts and participated in proliferation and migration. The present study tested the hypothesis that the transition of endothelial and epithelial cells to a mesenchymal phenotype was delineated by nestin expression. Three weeks following hypobaric hypoxia, adult male Sprague-Dawley rats characterized by alveolar and perivascular lung fibrosis were associated with increased nestin protein and mRNA levels and marked appearance of nestin/collagen type I((+))-fibroblasts. In the perivascular region of hypobaric hypoxic rats, displaced CD31((+))-endothelial cells were detected, exhibited a mesenchymal phenotype and co-expressed nestin. Likewise, epithelial cells in the lungs of hypobaric hypoxic rats transitioned to a mesenchymal phenotype distinguished by the co-expression of E-cadherin and collagen. Following the removal of FBS from primary passage rat alveolar epithelial cells, TGF-β1 was detected in the media and a subpopulation acquired a mesenchymal phenotype characterized by E-cadherin downregulation and concomitant induction of collagen and nestin. Bone morphogenic protein-7 treatment of alveolar epithelial cells prevented E-cadherin downregulation, suppressed collagen induction but partially inhibited nestin expression. These data support the premise that the transition of endothelial and epithelial cells to a mesenchymal cell may have contributed in part to the appearance nestin/collagen type I((+))-fibroblasts and the reactive fibrotic response in the lungs of hypobaric hypoxic rats.

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Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat

Cited by 16 publications

References 44 publications

Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells

Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression

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