DNMT3a negatively regulates PTEN to activate the PI3K/AKT pathway to aggravate renal fibrosis

Hu, Taotao; Chen, Fang; Chen, Dan; Liang, Hong‐Qing

doi:10.1016/j.cellsig.2022.110352

Cited by 11 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previously demonstrated that TGF‐β1 upregulated DNMT3A in fibroblasts SMAD dependently during the progression of systemic sclerosis 16 . DNMT3A is a de novo methyltransferase, which is upregulated in various fibrotic diseases, including EMs 14,15 . Herein, the TGF‐β1/SMAD3/DNMT3A regulatory axis was studied in EMs.…”

Section: Discussionmentioning

confidence: 95%

“…16 DNMT3A is a de novo methyltransferase, which is upregulated in various fibrotic diseases, including EMs. 14,15 Herein, the TGF-β1/SMAD3/DNMT3A regulatory axis was studied in EMs. Our results revealed that TGF-β1 increased RASAL1 is an inhibitor of Ras with a wide range of antifibrotic effects, and its overexpression can reduce collagen I and α-SMA expressions in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the role of DNMT3A in regulating fibrosis has been widely studied. As proof, Hu et al displayed that DNMT3A upregulation aggravated renal fibrosis by negatively regulating PTEN 15 . It was also reported that TGF‐β1 increased DNMT3A expression in fibroblasts in a small mothers against decapentaplegic (SMAD)‐dependent manner to promote the fibrosis process 16 .…”

Section: Introductionmentioning

confidence: 92%

“…As proof, Hu et al displayed that DNMT3A upregulation aggravated renal fibrosis by negatively regulating PTEN. 15 It was also reported that TGF-β1 increased DNMT3A expression in fibroblasts in a small mothers against decapentaplegic (SMAD)-dependent manner to promote the fibrosis process. 16 However, whether TGF-β1 can upregulate DNMT3A by acting on SMAD pathway in EMs and the role of DNMT3A in regulating fibrosis during EMs progression remain unknown.…”

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Feng,

Dong,

Tan

2023

J of Obstet and Gynaecol

View full text Add to dashboard Cite

BackgroundEndometrial‐derived stem cells are key players in endometriosis (EMs) pathogenesis, while the mechanism involved is still unclear. Herein, the role and regulatory mechanism of endometriotic mesenchymal stem cells (ecto‐MSCs) in regulating fibrosis during EMs progression were investigated.MethodsThe mRNA and protein expressions were assessed using qRT‐PCR, western blot, and immunofluorescence. Flow cytometry was adopted to analyze the markers of MSCs. Transwell assay was adopted to examine endometriotic stromal cells (ESCs) migration and invasion. The interactions between DNMT3A and RASAL1 were analyzed by ChIP assay. In addition, MSP was employed to detect RASAL1 promoter methylation level.ResultsEcto‐MSCs promoted ESCs migration, invasion, and fibrosis process by TGF‐β1 paracrine. It was subsequently revealed that TGF‐β1 upregulated DNMT3A in ESCs in a SMAD3‐dependent manner. As expected, DNMT3A knockdown abolished ecto‐MSCs' facilitation on ESCs migration, invasion, and fibrosis process. DNMT3A, as a methyltransferase, reduced RASAL1 expression in TGF‐β1‐treated ESCs by increasing RASAL1 promoter methylation level. RASAL1, as an antifibrotic protein, was lowly expressed in TGF‐β1‐treated ESCs, and its overexpression ameliorated TGF‐β1‐induced increase in ESCs migration, invasion, and fibrosis process.ConclusionTGF‐β1 secreted by ecto‐MSCs facilitated fibrogenesis in EMs through SMAD3/DNMT3A‐mediated RASAL1 inhibition.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Feng,

Dong,

Tan

2023

J of Obstet and Gynaecol

View full text Add to dashboard Cite

show abstract

“…Renal fibrosis, characterized by marked increased ECM deposition and activation of EMT is a hallmark of most of the CKD. Studies have reported that the activation of AKT signaling by miR-21 targeted PTEN downregulation leads to phenotypic alterations in tubular epithelial cells aggravating renal fibrosis [ 25 , 41 , 42 ]. Thus, to investigate the role of AKT signaling activation on renal fibrosis, we performed immunohistochemistry to evaluate the markers-fibronectin for ECM deposition and α-SMA for EMT initiation.…”

Section: Resultsmentioning

confidence: 99%

Prolonged Antibiotic Use in a Preclinical Model of Gulf War Chronic Multisymptom-Illness Causes Renal Fibrosis-like Pathology via Increased micro-RNA 21-Induced PTEN Inhibition That Is Correlated with Low Host Lachnospiraceae Abundance

Trivedi,

Bose,

Saha

et al. 2023

Cells

View full text Add to dashboard Cite

Gulf War (GW) veterans show gastrointestinal disturbances and gut dysbiosis. Prolonged antibiotic treatments commonly employed in veterans, especially the use of fluoroquinolones and aminoglycosides, have also been associated with dysbiosis. This study investigates the effect of prolonged antibiotic exposure on risks of adverse renal pathology and its association with gut bacterial species abundance in underlying GWI and aims to uncover the molecular mechanisms leading to possible renal dysfunction with aging. Using a GWI mouse model, administration of a prolonged antibiotic regimen involving neomycin and enrofloxacin treatment for 5 months showed an exacerbated renal inflammation with increased NF-κB activation and pro-inflammatory cytokines levels. Involvement of the high mobility group 1 (HMGB1)-mediated receptor for advanced glycation end products (RAGE) activation triggered an inflammatory phenotype and increased transforming growth factor-β (TGF-β) production. Mechanistically, TGF-β- induced microRNA-21 upregulation in the renal tissue leads to decreased phosphatase and tensin homolog (PTEN) expression. The above event led to the activation of protein kinase-B (AKT) signaling, resulting in increased fibronectin production and fibrosis-like pathology. Importantly, the increased miR-21 was associated with low levels of Lachnospiraceae in the host gut which is also a key to heightened HMGB1-mediated inflammation. Overall, though correlative, the study highlights the complex interplay between GWI, host gut dysbiosis, prolonged antibiotics usage, and renal pathology via miR-21/PTEN/AKT signaling.

show abstract

The role of PI3K/Akt signaling pathway in chronic kidney disease

Wang,

Gao,

Zhao

et al. 2024

Int Urol Nephrol

View full text Add to dashboard Cite

DNMT3a negatively regulates PTEN to activate the PI3K/AKT pathway to aggravate renal fibrosis

Cited by 11 publications

References 46 publications

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Prolonged Antibiotic Use in a Preclinical Model of Gulf War Chronic Multisymptom-Illness Causes Renal Fibrosis-like Pathology via Increased micro-RNA 21-Induced PTEN Inhibition That Is Correlated with Low Host Lachnospiraceae Abundance

The role of PI3K/Akt signaling pathway in chronic kidney disease

Contact Info

Product

Resources

About