IndraLab

Statements

PPARG binds USP42. 37 / 37
| 37
sparser
"Given the pivotal role of the USP42‐PPARγ axis in regulating liver regeneration, we have begun considering methods to target this molecular interplay as a basis for developing a novel therapeutic strategy."
40091484
sparser
"To activate the USP42‐PPARγ axis, it is essential to first induce the expression of USP42."
40091484
sparser
"More importantly, the USP42‐PPARγ axis can be activated by FGF2, which further guided us to establish a new extracellular vesicle‐based nanomedical strategy to target liver USP42‐PPARγ interaction and promote liver regeneration."
40091484
sparser
"FGF2 is An Activator for the USP42‐PPARγ Axis."
40091484
sparser
"The results described in the previous section raised the important question of whether the signaling factor upregulated USP42 levels and activated the USP42‐PPARγ axis during liver regeneration."
40091484
sparser
"Previous studies have shown that FGFs secreted by hepatocytes play a crucial role in mediating liver repair. [ xref ] Therefore, we speculated that FGFs activate the USP42‐PPARγ axis."
40091484
sparser
"The second step was to enhance the interaction between USP42 and PPARγ."
40091484
sparser
"To further determine whether FGF2 enhanced USP42‐PPARγ interaction, we performed Co‐IP in 293T and Hepa1‐6 cell models."
40091484
sparser
"Co‐IP assay demonstrated that TA indeed enhanced interaction between PPARγ and USP42 (Figure xref , Supporting Information)."
40091484
sparser
"To further confirm the regulatory role of the USP42‐PPARγ axis in liver repair, we used a specific PPARγ antagonist, GW9662, to inhibit PPARγ transcriptional activity in the presence of high USP42 expression 48 h after CCL4 treatment (Figure xref , Supporting Information)."
40091484
sparser
"Therefore, we speculated that the PPARγ ligand possibly possesses the ability to enhance the interaction of USP42 and PPARγ."
40091484
sparser
"In addition, fibroblast growth factor 2 (FGF2) initiated USP42 expression and enhanced the interaction between USP42 and PPARγ during the liver regeneration process."
40091484
sparser
"We then examined whether USP42 was associated with PPARγ."
40091484
sparser
"By applying this nanoparticle, the FGF2 and RSG could be delivered to liver tissue and activate the USP42‐PPARγ axis."
40091484
sparser
"This further supports the critical role of the USP42‐PPARγ signaling axis in liver repair."
40091484
sparser
"After 36 h of treatment, FGF2 increased PPARγ protein levels (Figure xref , Supporting Information), and markedly reinforced the interaction between USP42 and PPARγ (Figure xref , Supporting Information)."
40091484
sparser
"In Hepa1‐6 cells, endogenous USP42‐PPARγ interplay was also significantly enhanced by FGF2 (Figure xref , Supporting Information), and the ubiquitination level of PPARγ was simultaneously attenuated (Figure xref , Supporting Information)."
40091484
sparser
"USP42‐PPARγ Axis Controls the Redox Balance and Proliferation Activity in a Hepatocyte Model."
40091484
sparser
"RSG addition resulted in stronger binding of USP42 to PPARγ, indicating that the full agonist treatment was able to target and activate the USP42‐PPARγ axis (Figure xref , Supporting Information)."
40091484
sparser
"Since FGFR4 is the major FGF receptor expressed in hepatocytes, we tested the impact of FGFR4 inhibition on the USP42‐PPARγ interaction."
40091484
sparser
"Co‐IP results indicated that Rob administration effectively inhibited the association of USP42 with PPARγ (Figure xref , Supporting Information)."
40091484
sparser
"Next, to investigate the mechanism by which the USP42‐PPARγ axis controls the expression of antioxidative and proliferative genes, we constructed the USP42 overexpressed (USP42‐OE) and the USP42 knockdown (USP42‐KD) stable Hepa1‐6 cell lines."
40091484
sparser
"Moreover, the PPARγ full agonist, rosiglitazone (RSG), possesses the ability to further reinforce the USP42‐PPARγ interplay, which enlightens to construct of an extracellular vesicle‐based targeting strategy to activate the liver USP42‐PPARγ axis and promote liver regeneration."
40091484
sparser
"In summary, the work uncovers the importance of USP42‐PPARγ axis‐mediated liver tissue homeostasis and provides a promising regimen to target this protein‐protein interplay for liver regeneration."
40091484
sparser
"As shown in Figure  xref and Figure xref (Supporting Information), the C119A mutant inhibited the binding of USP42 to PPARγ, and correspondingly damaged the deubiquitylation effect of WT USP42 on PPARγ."
40091484
sparser
"We then used this siRNA to interfere with USP42 expression and tested the USP42‐PPARγ interaction."
40091484
sparser
"These data reveal that the USP42‐PPARγ axis determines the Hepa1‐6 cell proliferation."
40091484
sparser
"To further verify the activation role of FGF2 in the USP42‐PPARγ axis, an FGF2 neutralizing antibody was used to block FGF2 signaling in cell and animal models."
40091484
sparser
"FGF2 is the upstream signal that initiates and activates the USP42‐PPARγ axis."
40091484
sparser
"In the cell model, the effect of the USP42‐PPARγ axis on redox balance was also studied."
40091484
sparser
"Targeting the USP42‐PPARγ axis using EV@FGF2‐RSG efficiently protects against damage and promotes liver repair."
40091484
sparser
"The USP42‐PPARγ axis may be involved in the regulation of liver regeneration."
40091484
sparser
"These data indicate that endogenously secreted FGF2 activates the USP42‐PPARγ axis."
40091484
sparser
"Taken together, these results show that the USP42‐PPARγ axis controls redox balance and proliferation activity in hepatocytes."
40091484
sparser
"Collectively, these results suggest that FGF2 is an activator of the USP42‐PPARγ axis."
40091484
sparser
"USP42‐PPARγ Axis Inhibition Exacerbates Liver Damage and Delays Liver Regeneration."
40091484
sparser
"These data indicate that the USP42‐PPARγ axis in the liver was regulated by FGF2 in vivo."
40091484