Adenovirus-mediated P311 inhibits TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells &lt;i&gt;via&lt;/i&gt; TGF-β1-Smad-ILK pathway

Qi, Fanghua; Cai, Pingping; Liu, Xiang; Peng, Min; Si, Guomin

doi:10.5582/bst.2015.01129

Cited by 17 publications

(14 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, little is known regarding the roles performed by and regulation of EpMyT during skin wound healing. Recent studies using rat kidney epithelial cell lines have shown that P311 may promote IL-1α-induced EMT via a TGFβ1-independent pathway [31] and that it may inhibit TGFβ1-induced EMT by blocking the Smad/ILK pathways [32]. Furthermore, our recent in-vivo study showed that P311 promotes renal fibrosis via the TGFβ1/Smad signaling [33].…”

Section: Discussionmentioning

confidence: 98%

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

Yao

Wang

et al. 2016

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundEpithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling.MethodsWound healing and mesenchymal features were observed in the P311 KO and P311 WT mouse model of superficial second-degree burns. After the primary human or mouse EpSCs were forced to highly express P311 using an adenoviral vector, EpMyT was observed by immunofluorescence, real-time PCR, and western blot. The activity of TGFβ1 and Smad2/3 in EpSCs with different P311 levels was observed by western blot. The TβRI/II inhibitor LY2109761 and Smad3 siRNA were applied to block the EpMyT in P311-overexpressing EpSCs and exogenous TGFβ1 was to restore the EpMyT in P311 KO EpSCs. Furthermore, the mechanism of P311 regulating TGFβ1 was investigated by bisulfite sequencing PCR, luciferase activity assay, and real-time PCR.ResultsP311 KO mouse wounds showed delayed re-epithelialization and reduced mesenchymal features. The human or mouse EpSCs with overexpressed P311 exhibited fusiform morphological changes, upregulated expression of myofibroblast markers (α-SMA and vimentin), and downregulated expression of EpSC markers (β1-integrin and E-cadherin). P311-expressing EpSCs showed decreased TGFβ1 mRNA and increased TGFβ1 protein, TβRI/II mRNA, and activated Smad2/3. Moreover, LY2109761 and Smad3 siRNA reversed P311-induced EpMyT. Under the stimulation of exogenous TGFβ1, the phosphorylation of Smad2 and Smad3 in P311 KO EpSCs was significantly lower than that in P311 WT EpSCs and the EpMyT in P311 KO EpSCs was restored. Furthermore, P311 enhanced the methylation of TGFβ1 promoter and increased activities of TGFβ1 5′/3′ untranslated regions (UTRs) to stimulate TGFβ1 expression. P311+α-SMA+ cells and P311+vimentin+ cells were observed in the epidermis of human burn wounds. Also, P311 was upregulated by IL-1β, IL-6, TNFα, and hypoxia.ConclusionsP311 is a novel TGFβ1/Smad signaling-mediated regulator of transdifferentiation in EpSCs during cutaneous wound healing. Furthermore, P311 might stimulate TGFβ1 expression by promoting TGFβ1 promoter methylation and by activating the TGFβ1 5′/3′ UTR.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0421-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 98%

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

Yao

Wang

et al. 2016

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Although previous study has suggested P311 may be an important factor in myofibroblast transformation and in the progression of fibrosis, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown. In our previous studies, we found that P311 may be involved in the pathogenesis of renal fibrosis by inhibiting EMT process via TGF-β1-Smad-ILK pathway in NRK-52E cells (20). In the present study, we further examined the effect of P311 on TGF-β1-mediated EMT in a rat model of unilateral ureteral occlusion (UUO) renal fibrosis.…”

Section: Introductionmentioning

confidence: 86%

Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

Cai

Liu

et al. 2018

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown. In the present study, we examined the effect of P311 on transforming growth factor-β1 (TGF-β1)-mediated EMT in a rat model of unilateral ureteral occlusion (UUO) renal fibrosis. The recombinant adenovirus p311 (also called Ad-P311) was constructed and transferred it into UUO rats, the preventive effect and possible mechanism of P311 on TGF-β1-mediated EMT were explored. The UUO model was established successfully and Ad-P311 was administered into UUO rats each week for 4 weeks, then the serum levels of Cr, blood urea nitrogen (BUN) and albumin (ALB) were evaluated. H&E staining and Masson staining were performed to observe the pathological changes of kidneys. Immunohistochemical staining and western blot analysis were used to examine the EMT markers [E-cadherin and α-smooth muscle actin (α-SMA)], and signal transducers (p-Smad2/3 and Smad7). Integrin linked kinase (ILK) as a keyintracellular mediator that controls TGF-β1-mediated-EMT was also assayed by western blot analysis. The results showed that P311 could alleviate renal tubular damage and interstitial fibrosis improving Cr, BUN and ALB serum levels in UUO kidneys. Furthermore, P311 attenuated TGF-β1-mediated EMT through Smad-ILK signaling pathway with an increase in α-SMA, pSmad2/3 and ILK expression, and a decrease in E-cadherin and Smad7 expression in UUO kidneys. In conclusion, P311 may be involved in the pathogenesis of renal fibrosis by blocking TGF-β1-mediated EMT via TGF-β1-Smad-ILK pathway in UUO kidneys. P311 may be a novel target for the control of renal fibrosis and the progression of CKD.

show abstract

“…We also found P311 might be involved in the pathogenesis of renal fibrosis by inhibiting the EMT process via the TGF-β1-Smad-ILK pathway in vitro (23). Moreover, SDG combined with P311 could ameliorate renal fibrosis and block progression of CKD by regulating expression of the EMT-related protein α-SMA (24).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, P311 has proved to be of importance in the process of myofibroblast differentiation and fibrosis with functions of promoting embryonic development, wound healing, as well as nerve and lung regeneration, and so on (18)(19)(20)(21)(22). In our previous studies, we found that P311 might be involved in the pathogenesis of renal fibrosis by inhibiting the EMT process via the TGF-β1-Smad-ILK pathway in vitro (23). P311 might be a novel target for control of renal fibrosis and the progression of CKD.…”

Section: Introductionmentioning

confidence: 99%

“…Ad-P311 was constructed as described previously by the current authors and stored at -80°C for use (23). After establishment of the UUO model successfully, rats in the control group and UUO group were gavaged with 2 mL normal saline daily for 4 weeks and injected with 0.5 mL normal saline through tail vein each week for 4 weeks, while the rats in control + Ad-P311 group and UUO + Ad-P311 group were gavaged with 2 mL normal saline daily for 4 weeks and injected with 0.5 mL P311 adenovirus by tail vein each week for 4 weeks.…”

Section: Experimental Protocolmentioning

confidence: 99%

See 1 more Smart Citation

Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis <i>via</i> TGF-β1-Smad-ILK pathway

Cai

Liu

et al. 2017

BST

Self Cite

View full text Add to dashboard Cite

Adenovirus-mediated P311 inhibits TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells <i>via</i> TGF-β1-Smad-ILK pathway

Cited by 17 publications

References 22 publications

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis <i>via</i> TGF-β1-Smad-ILK pathway

Contact Info

Product

Resources

About