FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4309473604> ?p ?o ?g. }

• W4309473604 abstract "Histone acetylation/deacetylation play an essential role in modifying chromatin structure and in regulating cell plasticity in eukaryotic cells. Therefore, histone deacetylase (HDAC) pharmacological inhibitors are promising tools in the therapy of fibrotic diseases and in cancer. Peritoneal fibrosis is a pathological process characterized by many cellular and molecular alterations, including the acquisition of invasive/pro-fibrotic abilities by mesothelial cells (MCs) through induction of mesothelial to mesenchymal transition (MMT). The aim of this study was to characterize the molecular mechanism of the antifibrotic role of HDAC1 inhibition. Specifically, treatment with MS-275, an HDAC1-3 inhibitor previously known to promote MMT reversal, induced the expression of several TGFBRI mRNA-targeting miRNAs. Among them, miR-769-5p ectopic expression was sufficient to promote MMT reversal and to limit MC migration and invasion, whereas miR-769-5p silencing further enhanced mesenchymal gene expression. These results were confirmed by HDAC1 genetic silencing. Interestingly, miR-769-5p silencing maintained mesenchymal features despite HDAC1 inhibition, thus indicating that it is necessary to drive MMT reversal induced by HDAC1 inhibition. Besides TGFBRI, miR-769-5p was demonstrated to target SMAD2/3 and PAI-1 expression directly. When analyzing molecular mechanisms underlying miR-769-5p expression, we found that the transcription factor Wilms' tumor 1 (WT1), a master gene controlling MC development, binds to the miR-769-5p promoter favoring its expression. Interestingly, both WT1 expression and binding to miR-769-5p promoter were increased by HDAC1 inhibition and attenuated by TGFβ1 treatment. Finally, we explored the significance of these observations in the cell-to-cell communication: we evaluated the ability of miR-769-5p to be loaded into extracellular vesicles (EVs) and to promote MMT reversal in recipient mesenchymal-like MCs. Treatment of fibrotic MCs with EVs isolated from miR-769-5p over-expressing MCs promoted the down-regulation of specific mesenchymal targets and the reacquisition of an epithelial-like morphology. In conclusion, we highlighted an HDAC1-WT1-miR-769-5p axis potentially relevant for therapies aimed at counteracting organ fibrosis." @default.
• W4309473604 created "2022-11-28" @default.
• W4309473604 creator A5007482402 @default.
• W4309473604 creator A5011163857 @default.
• W4309473604 creator A5012553215 @default.
• W4309473604 creator A5012839091 @default.
• W4309473604 creator A5017097584 @default.
• W4309473604 creator A5017329858 @default.
• W4309473604 creator A5026359088 @default.
• W4309473604 creator A5026721434 @default.
• W4309473604 creator A5050274125 @default.
• W4309473604 creator A5056654136 @default.
• W4309473604 creator A5056950779 @default.
• W4309473604 creator A5063921848 @default.
• W4309473604 creator A5065735989 @default.
• W4309473604 creator A5084101516 @default.
• W4309473604 creator A5084138547 @default.
• W4309473604 date "2022-11-17" @default.
• W4309473604 modified "2023-10-18" @default.
• W4309473604 title "Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells" @default.
• W4309473604 cites W1925388323 @default.
• W4309473604 cites W1985844219 @default.
• W4309473604 cites W1995949067 @default.
• W4309473604 cites W2018303828 @default.
• W4309473604 cites W2065323571 @default.
• W4309473604 cites W2070856992 @default.
• W4309473604 cites W2072089208 @default.
• W4309473604 cites W2075950873 @default.
• W4309473604 cites W2082739830 @default.
• W4309473604 cites W2088876544 @default.
• W4309473604 cites W2099349169 @default.
• W4309473604 cites W2100891344 @default.
• W4309473604 cites W2139492356 @default.
• W4309473604 cites W2167510303 @default.
• W4309473604 cites W2175434446 @default.
• W4309473604 cites W2189757230 @default.
• W4309473604 cites W2210138065 @default.
• W4309473604 cites W2215419547 @default.
• W4309473604 cites W2262921329 @default.
• W4309473604 cites W2265947087 @default.
• W4309473604 cites W2339783540 @default.
• W4309473604 cites W2504182378 @default.
• W4309473604 cites W2530674994 @default.
• W4309473604 cites W2560659644 @default.
• W4309473604 cites W2592660965 @default.
• W4309473604 cites W2606524600 @default.
• W4309473604 cites W2610204288 @default.
• W4309473604 cites W2612551422 @default.
• W4309473604 cites W2775401927 @default.
• W4309473604 cites W2791362011 @default.
• W4309473604 cites W2805062009 @default.
• W4309473604 cites W2807007249 @default.
• W4309473604 cites W2888497093 @default.
• W4309473604 cites W2898106124 @default.
• W4309473604 cites W2900756811 @default.
• W4309473604 cites W2913361295 @default.
• W4309473604 cites W2922384241 @default.
• W4309473604 cites W2969578920 @default.
• W4309473604 cites W2980319025 @default.
• W4309473604 cites W2980506202 @default.
• W4309473604 cites W3039236515 @default.
• W4309473604 cites W3040017544 @default.
• W4309473604 cites W3065741572 @default.
• W4309473604 cites W3099265409 @default.
• W4309473604 cites W3196740152 @default.
• W4309473604 cites W3198151677 @default.
• W4309473604 cites W3204676945 @default.
• W4309473604 cites W3206711884 @default.
• W4309473604 cites W3216724973 @default.
• W4309473604 cites W4200370252 @default.
• W4309473604 cites W4281476456 @default.
• W4309473604 doi "https://doi.org/10.1038/s41419-022-05398-0" @default.
• W4309473604 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36396626" @default.
• W4309473604 hasPublicationYear "2022" @default.
• W4309473604 type Work @default.
• W4309473604 citedByCount "4" @default.
• W4309473604 countsByYear W43094736042023 @default.
• W4309473604 crossrefType "journal-article" @default.
• W4309473604 hasAuthorship W4309473604A5007482402 @default.
• W4309473604 hasAuthorship W4309473604A5011163857 @default.
• W4309473604 hasAuthorship W4309473604A5012553215 @default.
• W4309473604 hasAuthorship W4309473604A5012839091 @default.
• W4309473604 hasAuthorship W4309473604A5017097584 @default.
• W4309473604 hasAuthorship W4309473604A5017329858 @default.
• W4309473604 hasAuthorship W4309473604A5026359088 @default.
• W4309473604 hasAuthorship W4309473604A5026721434 @default.
• W4309473604 hasAuthorship W4309473604A5050274125 @default.
• W4309473604 hasAuthorship W4309473604A5056654136 @default.
• W4309473604 hasAuthorship W4309473604A5056950779 @default.
• W4309473604 hasAuthorship W4309473604A5063921848 @default.
• W4309473604 hasAuthorship W4309473604A5065735989 @default.
• W4309473604 hasAuthorship W4309473604A5084101516 @default.
• W4309473604 hasAuthorship W4309473604A5084138547 @default.
• W4309473604 hasBestOaLocation W43094736041 @default.
• W4309473604 hasConcept C104317684 @default.
• W4309473604 hasConcept C119056186 @default.
• W4309473604 hasConcept C119157956 @default.
• W4309473604 hasConcept C127561419 @default.
• W4309473604 hasConcept C142724271 @default.
• W4309473604 hasConcept C145059251 @default.

• next