Anti‐renal interstitial fibrosis effect of norcantharidin is exerted through inhibition of PP2Ac‐mediated C‐terminal phosphorylation of Smad3

Luo, Hanwen; Yin, Dandan; Zheng, Xiao; Wen, Lijun; Liao, Yingjun; Tang, Chengyuan; Zeng, Dong; Xiao, Hengting; Liu, Ying

doi:10.1111/cbdd.13781

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…Our previous studies demonstrated that NCTD could effectively prevent RIF both in vivo and in vitro 8 - 11 . Furthermore, we confirmed that NCTD prevented RIF via inhibiting the dephosphorylation of β-catenin and phosphorylation of Smad3 7 , 12 . However, the underlying mechanism responsible for the action of NCTD on RIF has yet to be fully elucidated.…”

Section: Introductionsupporting

confidence: 67%

NCTD Prevents Renal Interstitial Fibrosis via Targeting Sp1/lncRNA Gm26669 Axis

Tian¹,

Zheng²,

Wei³

et al. 2021

Int. J. Biol. Sci.

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In our previous study, we demonstrated that norcantharidin (NCTD) is a potential therapeutic agent for renal interstitial fibrosis (RIF). Recently, we found that lncRNA Gm26669 (Gm26669) contributed to the development of RIF and could be regulated by NCTD. However, the upstream mechanisms of Gm26669 and whether the anti-RIF effects of NCTD are related to its regulatory action on Gm26669 remain unclear. Our bioinformatics analysis indicated that special protein1 (Sp1), a transcription factor, may bind to the promoter of Gm26669. In the present study, we observed a significant increase in the nuclear translocation of Sp1 using both in vivo and in vitro models of RIF. Furthermore, the knockdown of Sp1 inhibited the expression of collagen type I (CoL-I) and fibronectin (Fn). Mechanistically, Sp1 promoted the expression levels of CoL-I and Fn by directly binding to the promoter of Gm26669 to elevate its expression level. Moreover, we found that NCTD alleviated RIF by inhibiting Gm26669 and the nuclear translocation of Sp1. Collectively, above results suggested that NCTD might prevent RIF via targeting the Sp1/Gm26669 axis, thus providing a new theoretical basis for the clinical application of NCTD in the treatment of RIF.

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Section: Introductionsupporting

confidence: 67%

NCTD Prevents Renal Interstitial Fibrosis via Targeting Sp1/lncRNA Gm26669 Axis

Tian¹,

Zheng²,

Wei³

et al. 2021

Int. J. Biol. Sci.

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“…Der PP2A-Inhibitor Norcantharidin, ein synthetisches Derivat von Cantharidin, hemmt das EMT-Programm und die EZM-Disposition in vitro (Li et al 2011;Li et al 2013). Durch die Applikation von Norcantharidin konnte in UUO-Mausmodellen und im Protein-Overload-Modell der Ratte eine Reduktion der renalen Fibrose demonstriert werden (Liu et al 2008;Li et al 2013;Luo et al 2021). Der antifibrotische Effekt von Norcantharidin beruht auf einer Abnahme der Phosphorylierung von SMAD2/3 und konsekutiver Expressionsreduktion des transkriptionellen EMT-Aktivators snail-family-transcriptional-repressor-1 (Snail-1) (Li et al 2013).…”

Section: Einfluss Der Pp2a-inhibition Auf Die Renale Fibrogeneseunclassified

“…Die hochregulierte Expression der fibroblastären PP2Acα begünstigt durch Suppression des extracellular-signal regulated kinases(ERK)-Signalwegs die TGF-β1-mediierte Fibroblastenaktivierung(Lu et al 2022). Die Dysregulation der PP2Ac-Aktivität führt zu einer aberranten Phosphorylierung von SMAD3 mit einer konsekutiven Transkription profibrotischer EZM-Zielgene(Meng et al 2015;Luo et al 2021).…”

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