Retraction Note to: Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice with experimental myocardial infarction partly through activating EGFR‑dependent pathway

Liu, Liang; Jin, Xian; Hu, Cui‐Fen; Zhang, Yaping; Zhou, Zhong’e; Li, Rong; Shen, Chengxing

doi:10.1007/s00395-022-00963-2

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eightweek-old male C57BL/6 Rag1 −/− mice obtained from Cyagen Biosciences were injected with Tregs to exam the effects of GPR174. Male C57BL/6 wild-type and Gpr174 −/Y mice aged 4 weeks were intravenously injected with adeno-associated viral (AAV9) bearing shRNA against AREG 38 (the shRNA sequence was 5′-CCACAAATATCCGGCTATATT-3′) to downregulate AREG expression in muscle tissues. All experiment animals were male for the character of less influence of sex hormone 39,40 .…”

Section: Experimental Animalsmentioning

confidence: 99%

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression

et al. 2022

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.

show abstract

Section: Experimental Animalsmentioning

confidence: 99%

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression

et al. 2022

View full text Add to dashboard Cite

show abstract

“…All ligands have been reported to be expressed in the heart and vasculature and for most ligands an involvement in cardiovascular pathologies has been shown. For example, HB-EGF plays a role in heart development and maintenance of cardiac function [15][16][17] , amphiregulin aggrevates cardiac fibrosis and dysfunction after myocardial infarction and is a potent mitogen for vascular smooth muscle cells (VSMCs) [18][19][20] , betacellulin enhances DNA synthesis and angiogenesis 20,21 and is located in atherosclerotic plaques of human aorta 22 and epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin 23 . Transforming growth factor-alpha mediates nuclear factor kappa B activation in strained arteries 24 .…”

mentioning

confidence: 99%

The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy

Stroedecke

Meinel

Markwardt

et al. 2021

Sci Rep

View full text Add to dashboard Cite

The EGF receptor (EGFR) has been extensively studied in tumor biology and recently a role in cardiovascular pathophysiology was suggested. The mineralocorticoid receptor (MR) is an important effector of the renin–angiotensin–aldosterone-system and elicits pathophysiological effects in the cardiovascular system; however, the underlying molecular mechanisms are unclear. Our aim was to investigate the importance of EGFR for MR-mediated cardiovascular pathophysiology because MR is known to induce EGFR expression. We identified a SNP within the EGFR promoter that modulates MR-induced EGFR expression. In RNA-sequencing and qPCR experiments in heart tissue of EGFR KO and WT mice, changes in EGFR abundance led to differential expression of cardiac ion channels, especially of the T-type calcium channel CACNA1H. Accordingly, CACNA1H expression was increased in WT mice after in vivo MR activation by aldosterone but not in respective EGFR KO mice. Aldosterone- and EGF-responsiveness of CACNA1H expression was confirmed in HL-1 cells by Western blot and by measuring peak current density of T-type calcium channels. Aldosterone-induced CACNA1H protein expression could be abrogated by the EGFR inhibitor AG1478. Furthermore, inhibition of T-type calcium channels with mibefradil or ML218 reduced diameter, volume and BNP levels in HL-1 cells. In conclusion the MR regulates EGFR and CACNA1H expression, which has an effect on HL-1 cell diameter, and the extent of this regulation seems to depend on the SNP-216 (G/T) genotype. This suggests that the EGFR may be an intermediate for MR-mediated cardiovascular changes and that SNP analysis can help identify subgroups of patients that will benefit most from MR antagonists.

show abstract

Retraction Note to: Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice with experimental myocardial infarction partly through activating EGFR‑dependent pathway

Cited by 2 publications

References 0 publications

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression

The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy

Contact Info

Product

Resources

About