| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-218 |
Sentence |
denotes |
The p65 subunit of NF-κB inhibits COL1A1 gene transcription in human dermal and scleroderma fibroblasts through its recruitment on promoter by protein interaction with transcriptional activators (c-Krox, Sp1, and Sp3). |
| T2 |
219-348 |
Sentence |
denotes |
Transcriptional mechanisms regulating type I collagen genes expression in physiopathological situations are not completely known. |
| T3 |
349-535 |
Sentence |
denotes |
In this study, we have investigated the role of nuclear factor-κB (NF-κB) transcription factor on type I collagen expression in adult normal human (ANF) and scleroderma (SF) fibroblasts. |
| T4 |
536-742 |
Sentence |
denotes |
We demonstrated that NF-κB, a master transcription factor playing a major role in immune response/apoptosis, down-regulates COL1A1 expression by a transcriptional control involving the -112/-61 bp sequence. |
| T5 |
743-907 |
Sentence |
denotes |
This 51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1) and Sp3, acting as trans-activators of type I collagen expression in ANF and SF. |
| T6 |
908-1085 |
Sentence |
denotes |
Knockdown of each one of these trans factors by siRNA confirmed the trans-activating effect of Sp1/Sp3 and the p65 subunit of NF-κB trans-inhibiting effect on COL1A1 expression. |
| T7 |
1086-1289 |
Sentence |
denotes |
Despite no existing κB consensus sequence in the COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-κB bind and/or are recruited on the proximal promoter in chromatin immunoprecipitation (ChIP) assays. |
| T8 |
1290-1565 |
Sentence |
denotes |
Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65 are necessary to mediate the NF-κB inhibitory effect on COL1A1 in ANF and SF were carried out; in this regard, immunoprecipitation assays revealed that they interact, and this was validated by re-ChIP. |
| T9 |
1566-1843 |
Sentence |
denotes |
Finally, the knockdown of Sp1/Sp3/c-Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF, suggesting that particular interactions are characteristic of the scleroderma phenotype. |
| T10 |
1844-2020 |
Sentence |
denotes |
In conclusion, our findings highlight a new mechanism for COL1A1 transcriptional regulation by NF-κB, and these data could allow the development of new antifibrotic strategies. |
