Glucagon-Like Peptide 1 Protects against Hyperglycemic-Induced Endothelial-to-Mesenchymal Transition and Improves Myocardial Dysfunction by Suppressing Poly(ADP-Ribose) Polymerase 1 Activity

Yan, Fei; Zhang, Guang-hao; Feng, Min; Zhang, Wei; Zhang, Jianing; Dong, Wenting; Zhang, Cheng; Zhang, Yun; Chen, Li; Zhang, Mingxiang

doi:10.2119/molmed.2014.00259

Cited by 31 publications

(24 citation statements)

References 40 publications

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“…24) TGF-β1 can induce endothelial cell proliferation and accelerate EndMT. 6) In mouse primary cultures of kidney endothelial cells, TGF-β1 timeand dose-dependently induced α-SMA expression along with loss of CD31 and vascular endothelial-cadherin expression. 25) Disturbed TGF-β activity results in a series of downstream consequences involving the prevention of myofibroblast differentiation, abolition of extracellular matrix synthesis, and intensified extracellular matrix degradation induced by matrix metalloproteinases.…”

Section: Discussionmentioning

confidence: 98%

“…16) Fibroblasts exist in the extracellular matrix of connective tissues with specific properties of mesenchymal cells, which may produce collagen proteins to constitute the extracellular matrix. 6) Renal fibrosis is chiefly generated by resident fibroblasts, nevertheless activated fibroblasts may originate from transdifferentiation of renal resident cells such as endothelial cells, called EndMT. 5) EndMT was previously considered a crucial procedure in cardiac development, but EndMT is now considered to also occur postnatally in diverse pathologic settings, involving tumour development, pulmonary hypertension, cardiac fibrosis and renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…4) During EndMT, endothelial cells eliminate endothelial markers, such as cluster of differentiation 31 (CD31) and vascular endothelial-cadherin, and acquire mesenchymal markers, such as fibroblast-specific protein 1 and α-smooth muscle actin (α-SMA). 5,6) Previous studies have indicated that diabetic cardiac and renal fibrosis were related to EndMT, and inhibition of EndMT could prevent cardiac and renal fibrosis. 7) Transforming growth factor-β (TGF-β) is a major promoting cytokine of renal fibrosis.…”

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confidence: 99%

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Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Guo

Cai

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

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There may be cardio-renal interactions in rats of isoproterenol-induced heart failure, which may be associated with renal fibrosis and endothelial-to-mesenchymal transition (EndMT). Since its discovery, relaxin (RLX) which was regarded as a reproductive hormone for a long time, is recently considered an effective antifibrotic hormone in cardiac and renal fibrosis. We studied whether RLX diminished renal fibrosis in rats of isoproterenol (Iso)-induced heart failure and investigated the mechanism. Fifty male Sprague-Dawley rats were separated into five groups for treatment: control; Iso subcutaneously injection to induce heart failure, which led to renal fibrosis; RLX subcutaneously injection at low, medium and high dose (0.2, 2, 20 µg·kg·d for 21 d). Indices of cardiac function and organ fibrosis were examined. Expression and changes in levels of collagen, cluster of differentiation 31 (CD31), α-smooth muscle actin (SMA), and transforming growth factor β (TGF-β) were measured in renal tissues. In rats with heart failure induced by Iso, treatment with RLX significantly ameliorated cardiac function and inhibited cardiac and renal fibrosis. RLX decreased renal collagen types I and III deposition, increased CD31 expression, and decreased the expression of α-SMA and TGF-β, thereby possibly indicating inhibited renal EndMT in kidneys. Iso-induced heart and renal fibrosis was inhibited even greater with high-dose RLX, so the antifibrotic effect of RLX may be dose-related. In conclusion, RLX may ameliorate renal fibrosis in rats of Iso-induced heart failure, and it is infered that prevention of the EndMT may be one of the possible potential signaling pathways.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Guo

Cai

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Whole‐cell proteins were isolated from cell lysates and freshly dissected mice hearts. Western blot analysis was performed as described . PVDF membranes were incubated with primary antibodies against PHD3 (1:500; Novus Biologicals, Littleton, CO), HIF‐1α (1:1000; Cell Signaling Technology, Danvers, MA), CD31 (1:1000; Abcam), VE‐cadherin (1:1000; Cell Signaling Technology), α‐SMA (1:500; Abcam), FSP‐1 (1:250; Abcam), Snail (1:500; Cell Signaling Technology), Twist (1:500; Abcam), Collagen I (1:5000; Abcam), Collagen III (1:5000; Abcam), and β‐actin (1:1000; Abcam).…”

Section: Methodsmentioning

confidence: 99%

Prolyl 4‐Hydroxylase Domain Protein 3 Overexpression Improved Obstructive Sleep Apnea—Induced Cardiac Perivascular Fibrosis Partially by Suppressing Endothelial‐to‐Mesenchymal Transition

Zhang

et al. 2017

JAHA

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BackgroundIntermittent hypoxia (IH) induced by obstructive sleep apnea is the key factor involved in cardiovascular fibrosis. Under persistent hypoxia condition, endothelial cells respond by endothelial‐to‐mesenchymal transition (EndMT), which is associated with cardiovascular fibrosis. Prolyl 4‐hydroxylase domain protein 3 (PHD3) is a cellular oxygen sensor and its expression increased in hypoxia. However, its role in obstructive sleep apnea–induced EndMT and cardiovascular fibrosis is still uncertain. We investigated the potential mechanism of obstructive sleep apnea–induced cardiac perivascular fibrosis and the role of PHD3 in it.Methods and ResultsIn vivo, C56BL/6 mice were exposed to IH for 12 weeks. PHD3 expression was changed by lentivirus‐mediated short‐hairpin PHD3 and lentivirus carrying PHD3 cDNA. EndMT related protein levels, histological and functional parameters were detected after 12 weeks. In vitro, human umbilical vein endothelial cells were treated with IH/short‐hairpin PHD3/lentivirus carrying PHD3 cDNA to explore the mechanism of PHD3 in altered function of human umbilical vein endothelial cells. We found that chronic intermittent hypoxia increase PHD3 expression and EndMT. In vivo, IH accelerate cardiac dysfunction and aggravate collagen deposition via the process of EndMT. And, when PHD3 were overexpressed, cardiac dysfunction and collagen excessive deposition were improved. In vitro, IH induced EndMT, which endow human umbilical vein endothelial cells spindle morphology and an enhanced ability to migration and collagen secretion. PHD3 overexpression in cultured human umbilical vein endothelial cells ameliorated IH–induced EndMT through inactivating hypoxia‐inducible factor 1 alpha and small mothers against decapentaplegic 2 and 3.ConclusionsObstructive sleep apnea–induced cardiac perivascular fibrosis is associated with EndMT, and PHD3 overexpression might be beneficial in the prevention of it by inhibiting EndMT. PHD3 overexpression might have therapeutic potential in the treatment of the disease.

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“…As an extension to that, several nutrient sensor pathways were shown to be mediated by PARP-1. PARP-1 influences the phophatidil-inositol-3 kinase (PI3K)-Akt and glucagon-like peptide (GLP)-1 pathway through which PARP-1 mediates insulin (and probably growth factor) signaling [53][54][55][56]. There are numerous examples where PARPs interact with nuclear receptors and hence mediate sensing intra or extracellular lipid levels [8].…”

Section: Deregulated Nutrient Sensingmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Vida¹,

Abdul‐Rahman²,

Mikó³

et al. 2016

CPPS

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Glucagon-Like Peptide 1 Protects against Hyperglycemic-Induced Endothelial-to-Mesenchymal Transition and Improves Myocardial Dysfunction by Suppressing Poly(ADP-Ribose) Polymerase 1 Activity

Cited by 31 publications

References 40 publications

Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Prolyl 4‐Hydroxylase Domain Protein 3 Overexpression Improved Obstructive Sleep Apnea—Induced Cardiac Perivascular Fibrosis Partially by Suppressing Endothelial‐to‐Mesenchymal Transition

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

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