Wnt/β-Catenin Inhibitor Dickkopf 1

Reinhold, Stefan; Blankesteijn, W. Matthijs

doi:10.1161/atvbaha.118.312144

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…DKK1 is recognized as an inhibitor of the canonical WNT/β-catenin signaling pathway. 6 , 20 , 21 Platelets are the main source of circulating DKK1, and an increase in DKK1 leads to the formation of leukocyte-platelet aggregates (LPA), which facilitates leukocyte infiltration. 22 In the lung, DKK1 promotes macrophage and neutrophil infiltration by inhibiting the WNT pathway, and the infiltration of inflammatory cells is alleviated after inhibition of DKK1.…”

Section: Discussionmentioning

confidence: 99%

DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

Dai

Wan

et al. 2022

COPD

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Purpose WNT/β-catenin signal pathway is a potential hope for lung tissue repair. We investigated the levels of Dickkopf‐1 (DKK1), an endogenous inhibitor of WNT/β-catenin signal pathway, in chronic obstructive pulmonary disease (COPD) patients and airway inflammation. Patients and Methods Collected the demographic and clinical characteristics of 36 healthy controls, 25 stable COPD patients and 10 acute exacerbation of COPD (AECOPD) patients, then performed pulmonary function and detected serum DKK1 levels. After over-expression of DKK1, detect the levels of DDK1, lipoprotein-related protein 6 (LRP6) and inflammatory factors in bronchial epithelial cells stimulated with cigarette smoke extract (CSE). Results Serum DKK1 were reduced in stable COPD patients compared to healthy controls (3866.72 ± 775.33 pg/mL vs 5317.61 ± 1317.20 pg/mL, p<0.0001), but there was no significant difference between stable and acutely exacerbated patients (3866.72 ± 775.33 pg/mL vs 3482.10 ± 841.25 pg/mL, p>0.05). DKK1 was positively correlated with FEV1 (r = 0.570, p<0.0001), FEV1/FVC (rho = 0.590, p<0.0001), FEV1/Pre (r = 0.517, p<0.0001). Multiple linear regression analysis also suggested that FEV1 levels were higher with increasing DKK1. In vitro, elevated IL-6, IL-8, TNF-α and decreased DKK1, LRP6 were found in Beas-2B cells after CSE treatments, and increased LRP6 and decreased inflammatory factors were found after overexpression of DKK1. Andrographolide restored the CSE-induced decrease in DKK1 and increase in IL-6 and IL-8. Conclusion DKK1 levels were decreased in COPD patients and positively correlated with lung function, overexpression of DKK1 and andrographolide attenuated airway cell inflammation, both suggesting a potential role in pathophysiology and providing a disease-specific biomarker pattern.

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Section: Discussionmentioning

confidence: 99%

DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

Dai

Wan

et al. 2022

COPD

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“…Wnt signaling pathway activation also contributed to functional recovery and increased neuroprotective processes and neurogenesis after cerebral ischemia [36]. As an antagonist of the Wnt pathway, Dkk1 prevents Wnt activation by binding to the Wnt receptor, leading to the activation of the Wnt/β-catenin signaling pathway [37]. Recent studies showed that Dkk1 is potentially induced in the hippocampal CA1 area after global cerebral ischemia, and administration of Dkk1 antisense oligonucleotides protects the CA1 region against cerebral ischemia-induced neuronal death [38].…”

Section: Discussionmentioning

confidence: 99%

Lithium chloride promotes neural functional recovery after local cerebral ischaemia injury in rats through Wnt signalling pathway activation

Jun-de

Tingting

et al. 2023

Folia Morphol

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“…The role of the DKK protein and secreted frizzled-related protein (sFRP) family in bone development, atherosclerosis and VC has been discussed in detail recently [76][77][78]. For this reason, we will further address the relationship between WNT inhibitors and VC in the following chapter.…”

Section: The Role Of Wnt Inhibitorsmentioning

confidence: 99%

The Interplay of WNT and PPARγ Signaling in Vascular Calcification

Reinhold

Blankesteijn

Foulquier

2020

Cells

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Vascular calcification (VC), the ectopic deposition of calcium phosphate crystals in the vessel wall, is one of the primary contributors to cardiovascular death. The pathology of VC is determined by vascular topography, pre-existing diseases, and our genetic heritage. VC evolves from inflammation, mediated by macrophages, and from the osteochondrogenic transition of vascular smooth muscle cells (VSMC) in the atherosclerotic plaque. This pathologic transition partly resembles endochondral ossification, involving the chronologically ordered activation of the β-catenin-independent and -dependent Wingless and Int-1 (WNT) pathways and the termination of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction. Several atherosclerotic plaque studies confirmed the differential activity of PPARγ and the WNT signaling pathways in VC. Notably, the actively regulated β-catenin-dependent and -independent WNT signals increase the osteochondrogenic transformation of VSMC through the up-regulation of the osteochondrogenic transcription factors SRY-box transcription factor 9 (SOX9) and runt-related transcription factor 2 (RUNX2). In addition, we have reported studies showing that WNT signaling pathways may be antagonized by PPARγ activation via the expression of different families of WNT inhibitors and through its direct interaction with β-catenin. In this review, we summarize the existing knowledge on WNT and PPARγ signaling and their interplay during the osteochondrogenic differentiation of VSMC in VC. Finally, we discuss knowledge gaps on this interplay and its possible clinical impact.

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Wnt/β-Catenin Inhibitor Dickkopf 1

Cited by 9 publications

References 28 publications

DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

Lithium chloride promotes neural functional recovery after local cerebral ischaemia injury in rats through Wnt signalling pathway activation

The Interplay of WNT and PPARγ Signaling in Vascular Calcification

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