BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells (2024)

Chen, P. J., Kuo, L. M., Wu, Y. H., Chang, Y. C., Lai, K. H. (2020). BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells. Biomedicines, 8(9), Article 330. https://doi.org/10.3390/biomedicines8090330

Chen, Po Jen ; Kuo, Liang Mou ; Wu, Yi Hsiu et al. / BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells. In: Biomedicines. 2020 ; Vol. 8, No. 9.

@article{c70c5e5d5a0748249311c4f673bc6639,

title = "BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells",

abstract = "Activation of hepatic stellate cells (HSCs) is a critical pathogenic feature of liver fibrosis and cirrhosis. BAY 41-2272 is a canonical non-nitric oxide (NO)-based soluble guanylyl cyclase (sGC) stimulator that triggers cyclic guanosine monophosphate (cGMP) signaling for attenuation of fibrotic disorders; however, the impact of BAY 41-2272 on HSC activation remains ill-defined. Transforming growth factor (TGF)Β and its downstream connective tissue growth factor (CTGF or cellular communication network factor 2, CCN2) are critical fibrogenic cytokines for accelerating HSC activation. Here, we identified that BAY 41-2272 significantly inhibited the TGF{\ss}1-induced mRNA and protein expression of CTGF in mouse primary HSCs. Indeed, BAY 41-2272 increased the sGC activity and cGMP levels that were potentiated by two NO donors and inhibited by a specific sGC inhibitor, ODQ. Surprisingly, the inhibitory effects of BAY 41-2272 on CTGF expression were independent of the sGC/cGMP pathway in TGFΒ1-activated primary HSCs. BAY 41-2272 selectively restricted the TGFΒ1-induced phosphorylation of Akt but not canonical Smad2/3 in primary HSCs. Together, we illustrate a unique framework of BAY 41-2272 for inhibiting TGFΒ1-induced CTGF upregulation and HSC activation via a noncanonical Akt-dependent but sGC/cGMP-independent pathway.",

keywords = "Akt, BAY 41-2272, CTGF, Hepatic stellate cell, sGC",

author = "Chen, {Po Jen} and Kuo, {Liang Mou} and Wu, {Yi Hsiu} and Chang, {Yu Chia} and Lai, {Kuei Hung} and Hwang, {Tsong Long}",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors.",

year = "2020",

month = sep,

doi = "10.3390/biomedicines8090330",

language = "英语",

volume = "8",

journal = "Biomedicines",

issn = "2227-9059",

number = "9",

}

Chen, PJ, Kuo, LM, Wu, YH, Chang, YC, Lai, KH 2020, 'BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells', Biomedicines, vol. 8, no. 9, 330. https://doi.org/10.3390/biomedicines8090330

BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells. / Chen, Po Jen; Kuo, Liang Mou; Wu, Yi Hsiu et al.
In: Biomedicines, Vol. 8, No. 9, 330, 09.2020.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells

AU - Chen, Po Jen

AU - Kuo, Liang Mou

AU - Wu, Yi Hsiu

AU - Chang, Yu Chia

AU - Lai, Kuei Hung

AU - Hwang, Tsong Long

N1 - Publisher Copyright:© 2020 by the authors.

PY - 2020/9

Y1 - 2020/9

N2 - Activation of hepatic stellate cells (HSCs) is a critical pathogenic feature of liver fibrosis and cirrhosis. BAY 41-2272 is a canonical non-nitric oxide (NO)-based soluble guanylyl cyclase (sGC) stimulator that triggers cyclic guanosine monophosphate (cGMP) signaling for attenuation of fibrotic disorders; however, the impact of BAY 41-2272 on HSC activation remains ill-defined. Transforming growth factor (TGF)Β and its downstream connective tissue growth factor (CTGF or cellular communication network factor 2, CCN2) are critical fibrogenic cytokines for accelerating HSC activation. Here, we identified that BAY 41-2272 significantly inhibited the TGFß1-induced mRNA and protein expression of CTGF in mouse primary HSCs. Indeed, BAY 41-2272 increased the sGC activity and cGMP levels that were potentiated by two NO donors and inhibited by a specific sGC inhibitor, ODQ. Surprisingly, the inhibitory effects of BAY 41-2272 on CTGF expression were independent of the sGC/cGMP pathway in TGFΒ1-activated primary HSCs. BAY 41-2272 selectively restricted the TGFΒ1-induced phosphorylation of Akt but not canonical Smad2/3 in primary HSCs. Together, we illustrate a unique framework of BAY 41-2272 for inhibiting TGFΒ1-induced CTGF upregulation and HSC activation via a noncanonical Akt-dependent but sGC/cGMP-independent pathway.

AB - Activation of hepatic stellate cells (HSCs) is a critical pathogenic feature of liver fibrosis and cirrhosis. BAY 41-2272 is a canonical non-nitric oxide (NO)-based soluble guanylyl cyclase (sGC) stimulator that triggers cyclic guanosine monophosphate (cGMP) signaling for attenuation of fibrotic disorders; however, the impact of BAY 41-2272 on HSC activation remains ill-defined. Transforming growth factor (TGF)Β and its downstream connective tissue growth factor (CTGF or cellular communication network factor 2, CCN2) are critical fibrogenic cytokines for accelerating HSC activation. Here, we identified that BAY 41-2272 significantly inhibited the TGFß1-induced mRNA and protein expression of CTGF in mouse primary HSCs. Indeed, BAY 41-2272 increased the sGC activity and cGMP levels that were potentiated by two NO donors and inhibited by a specific sGC inhibitor, ODQ. Surprisingly, the inhibitory effects of BAY 41-2272 on CTGF expression were independent of the sGC/cGMP pathway in TGFΒ1-activated primary HSCs. BAY 41-2272 selectively restricted the TGFΒ1-induced phosphorylation of Akt but not canonical Smad2/3 in primary HSCs. Together, we illustrate a unique framework of BAY 41-2272 for inhibiting TGFΒ1-induced CTGF upregulation and HSC activation via a noncanonical Akt-dependent but sGC/cGMP-independent pathway.

KW - Akt

KW - BAY 41-2272

KW - CTGF

KW - Hepatic stellate cell

KW - sGC

UR - http://www.scopus.com/inward/record.url?scp=85090762621&partnerID=8YFLogxK

U2 - 10.3390/biomedicines8090330

DO - 10.3390/biomedicines8090330

M3 - 文章

AN - SCOPUS:85090762621

SN - 2227-9059

VL - 8

JO - Biomedicines

JF - Biomedicines

IS - 9

M1 - 330

ER -

Chen PJ, Kuo LM, Wu YH, Chang YC, Lai KH, Hwang TL. BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFΒ1-activated hepatic stellate cells. Biomedicines. 2020 Sep;8(9):330. doi: 10.3390/biomedicines8090330