Down-regulation of miR-204 attenuates endothelial-mesenchymal transition by enhancing autophagy in hypoxia-induced pulmonary hypertension

Liu, Ting; Zou, Xingfu; Huang, Ning; Ge, Xinlan; Yao, Mao-Zhong; Hong, Liang; Zhang, Zheng; Hu, Chang-Ping

doi:10.1016/j.ejphar.2019.172673

Cited by 27 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides contributing to the distinct above-mentioned mechanisms, HIF-1a is able to bind the hypoxia-response element of TWIST proximal promoter and mediate its expression (156). Twist and Snail are targets of b-catenin signaling (156,157), and are known EMT transcription factors (158), whose levels can be controlled by MA (159). In GBM particularly, a recent report describes the associated increase in MA markers with decreased levels of Twist and Snail in tumor cells treated with a combination of TMZ and curcumin (160).…”

Section: Crosstalk Between Autophagy Epithelial-mesenchymal Transitimentioning

confidence: 99%

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

et al. 2020

View full text Add to dashboard Cite

Section: Crosstalk Between Autophagy Epithelial-mesenchymal Transitimentioning

confidence: 99%

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

et al. 2020

View full text Add to dashboard Cite

“…To test whether EndMT could be involved in PHV, the endothelial cell adhesion molecule CD31 [ 35 ] was investigated. Interestingly, immunohistochemistry revealed a relative decrease in the intensity of CD31 staining in the endothelium of PHV biopsies, as compared to control and PD-treated patients who did not develop submesothelial arteriolopathy ( Figure 4 A) which was also confirmed by immunofluorescence ( Figure S1A ).…”

Section: Resultsmentioning

confidence: 99%

“…In fact, the function of the vascular cell adhesion and signaling molecule, CD31, in endothelial cells, has been related to vascular permeability barrier preservation. At the same time, CD31 supports the integrity of endothelial cell–cell junctions and provide protection from the microvascular network [ 35 ]. While not clearly documented, it is tempting to speculate that many of the molecular and phenotypic changes described for other transitional programs (e.g., EMT or MMT), could also play critical roles in orchestrating an EndMT process [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

Díaz

Sandoval

Rodrigues-Díez

et al. 2020

IJMS

View full text Add to dashboard Cite

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.

show abstract

“…Extensive studies have shown that the transformation into activated fibroblasts is an extremely complex process involving numerous signaling pathways and that depends on the physiological or pathological status of the cells and on their specific cellular contexts [ 44 ]. Among these, recent studies indicate that mTOR and the substrate of autophagy SQSTM1/p62 contribute to mesenchymal transition and that autophagy enhancers can attenuate fibroblast activation [ 29 , 44 , 46 ]. Moreover, the NF-κB pathway also plays an important role in inducing a myofibroblast-like phenotype, especially under inflammatory conditions, elicited for instance by TNF-α or IL-6 [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis

Milani

Mammarella

Rossi

et al. 2021

J Neuroinflammation

View full text Add to dashboard Cite

Background An increasing number of studies evidences that amyotrophic lateral sclerosis (ALS) is characterized by extensive alterations in different cell types and in different regions besides the CNS. We previously reported the upregulation in ALS models of a gene called fibroblast-specific protein-1 or S100A4, recognized as a pro-inflammatory and profibrotic factor. Since inflammation and fibrosis are often mutual-sustaining events that contribute to establish a hostile environment for organ functions, the comprehension of the elements responsible for these interconnected pathways is crucial to disclose novel aspects involved in ALS pathology. Methods Here, we employed fibroblasts derived from ALS patients harboring the C9orf72 hexanucleotide repeat expansion and ALS patients with no mutations in known ALS-associated genes and we downregulated S100A4 using siRNA or the S100A4 transcriptional inhibitor niclosamide. Mice overexpressing human FUS were adopted to assess the effects of niclosamide in vivo on ALS pathology. Results We demonstrated that S100A4 underlies impaired autophagy and a profibrotic phenotype, which characterize ALS fibroblasts. Indeed, its inhibition reduces inflammatory, autophagic, and profibrotic pathways in ALS fibroblasts, and interferes with different markers known as pathogenic in the disease, such as mTOR, SQSTM1/p62, STAT3, α-SMA, and NF-κB. Importantly, niclosamide in vivo treatment of ALS-FUS mice reduces the expression of S100A4, α-SMA, and PDGFRβ in the spinal cord, as well as gliosis in central and peripheral nervous tissues, together with axonal impairment and displays beneficial effects on muscle atrophy, by promoting muscle regeneration and reducing fibrosis. Conclusion Our findings show that S100A4 has a role in ALS-related mechanisms, and that drugs such as niclosamide which are able to target inflammatory and fibrotic pathways could represent promising pharmacological tools for ALS.

show abstract

Down-regulation of miR-204 attenuates endothelial-mesenchymal transition by enhancing autophagy in hypoxia-induced pulmonary hypertension

Cited by 27 publications

References 29 publications

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis

Contact Info

Product

Resources

About