Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313702012> ?p ?o ?g. }
- W4313702012 abstract "Abstract Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet the molecular mechanisms governing their crosstalk are poorly understood. In diseased organs, stress-induced changes in gene expression fuel maladaptive cell state transitions and pathological interaction between diverse cellular compartments. Although chronic fibroblast activation worsens dysfunction of lung, liver, kidney, and heart, and exacerbates many cancers, the stress-sensing mechanisms initiating the transcriptional activation of fibroblasts are not well understood. Here, we show that conditional deletion of the transcription co-activator Brd4 in Cx3cr1 -positive myeloid cells ameliorates heart failure and is associated with a dramatic reduction in fibroblast activation. Analysis of single-cell chromatin accessibility and BRD4 occupancy in vivo in Cx3cr1 -positive cells identified a large enhancer proximal to Interleukin-1 beta (Il1b) , and a series of CRISPR deletions revealed the precise stress-dependent regulatory element that controlled expression of Il1b in disease. Secreted IL1B functioned non-cell autonomously to activate a p65/RELA-dependent enhancer near the transcription factor MEOX1 , resulting in a profibrotic response in human cardiac fibroblasts. In vivo , antibody-mediated IL1B neutralization prevented stress-induced expression of MEOX1 , inhibited fibroblast activation, and improved cardiac function in heart failure. The elucidation of BRD4-dependent crosstalk between a specific immune cell subset and fibroblasts through IL1B provides new therapeutic strategies for heart disease and other disorders of chronic inflammation and maladaptive tissue remodeling." @default.
- W4313702012 created "2023-01-08" @default.
- W4313702012 creator A5000381401 @default.
- W4313702012 creator A5003567291 @default.
- W4313702012 creator A5005062415 @default.
- W4313702012 creator A5007489781 @default.
- W4313702012 creator A5014294195 @default.
- W4313702012 creator A5016348069 @default.
- W4313702012 creator A5020063989 @default.
- W4313702012 creator A5020588442 @default.
- W4313702012 creator A5024863554 @default.
- W4313702012 creator A5027205843 @default.
- W4313702012 creator A5030143382 @default.
- W4313702012 creator A5046287902 @default.
- W4313702012 creator A5047722883 @default.
- W4313702012 creator A5049693824 @default.
- W4313702012 creator A5050880800 @default.
- W4313702012 creator A5055939902 @default.
- W4313702012 creator A5065804918 @default.
- W4313702012 creator A5068350489 @default.
- W4313702012 creator A5072886690 @default.
- W4313702012 creator A5074855154 @default.
- W4313702012 creator A5075358012 @default.
- W4313702012 creator A5081249989 @default.
- W4313702012 creator A5089239318 @default.
- W4313702012 creator A5090739168 @default.
- W4313702012 date "2023-01-07" @default.
- W4313702012 modified "2023-10-18" @default.
- W4313702012 title "Chromatin Remodeling Drives Immune-Fibroblast Crosstalk in Heart Failure Pathogenesis" @default.
- W4313702012 cites W1565539350 @default.
- W4313702012 cites W1971578941 @default.
- W4313702012 cites W1977281942 @default.
- W4313702012 cites W2002730815 @default.
- W4313702012 cites W2010484682 @default.
- W4313702012 cites W2014677321 @default.
- W4313702012 cites W2015582983 @default.
- W4313702012 cites W2041535798 @default.
- W4313702012 cites W2095525101 @default.
- W4313702012 cites W2107915827 @default.
- W4313702012 cites W2114104545 @default.
- W4313702012 cites W2135647797 @default.
- W4313702012 cites W2146512944 @default.
- W4313702012 cites W2153406260 @default.
- W4313702012 cites W2154924534 @default.
- W4313702012 cites W2156101280 @default.
- W4313702012 cites W2616008841 @default.
- W4313702012 cites W2735527928 @default.
- W4313702012 cites W2748400555 @default.
- W4313702012 cites W2750808153 @default.
- W4313702012 cites W2754708254 @default.
- W4313702012 cites W2789956380 @default.
- W4313702012 cites W2803237856 @default.
- W4313702012 cites W2900002398 @default.
- W4313702012 cites W2901646806 @default.
- W4313702012 cites W2902050841 @default.
- W4313702012 cites W2904624968 @default.
- W4313702012 cites W2927400066 @default.
- W4313702012 cites W2950464315 @default.
- W4313702012 cites W2952643930 @default.
- W4313702012 cites W2967233606 @default.
- W4313702012 cites W2982287350 @default.
- W4313702012 cites W2990914781 @default.
- W4313702012 cites W3031596611 @default.
- W4313702012 cites W3039832648 @default.
- W4313702012 cites W3093674907 @default.
- W4313702012 cites W3096166596 @default.
- W4313702012 cites W3121466164 @default.
- W4313702012 cites W3131634425 @default.
- W4313702012 cites W3145969289 @default.
- W4313702012 cites W3163348136 @default.
- W4313702012 cites W3176137376 @default.
- W4313702012 cites W3192531502 @default.
- W4313702012 cites W4205403685 @default.
- W4313702012 cites W4205428045 @default.
- W4313702012 cites W4213015374 @default.
- W4313702012 cites W4220667894 @default.
- W4313702012 cites W4226426895 @default.
- W4313702012 cites W4290989128 @default.
- W4313702012 doi "https://doi.org/10.1101/2023.01.06.522937" @default.
- W4313702012 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36711864" @default.
- W4313702012 hasPublicationYear "2023" @default.
- W4313702012 type Work @default.
- W4313702012 citedByCount "2" @default.
- W4313702012 countsByYear W43137020122023 @default.
- W4313702012 crossrefType "posted-content" @default.
- W4313702012 hasAuthorship W4313702012A5000381401 @default.
- W4313702012 hasAuthorship W4313702012A5003567291 @default.
- W4313702012 hasAuthorship W4313702012A5005062415 @default.
- W4313702012 hasAuthorship W4313702012A5007489781 @default.
- W4313702012 hasAuthorship W4313702012A5014294195 @default.
- W4313702012 hasAuthorship W4313702012A5016348069 @default.
- W4313702012 hasAuthorship W4313702012A5020063989 @default.
- W4313702012 hasAuthorship W4313702012A5020588442 @default.
- W4313702012 hasAuthorship W4313702012A5024863554 @default.
- W4313702012 hasAuthorship W4313702012A5027205843 @default.
- W4313702012 hasAuthorship W4313702012A5030143382 @default.
- W4313702012 hasAuthorship W4313702012A5046287902 @default.
- W4313702012 hasAuthorship W4313702012A5047722883 @default.
- W4313702012 hasAuthorship W4313702012A5049693824 @default.
- W4313702012 hasAuthorship W4313702012A5050880800 @default.