Next Article in Journal
Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
Previous Article in Journal
Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts
Article

P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation

by 1,2,3,4, 1,2,3,4, 1,2,3, 1,5, 2,3,6, 2,7, 1,8, 8 and 1,2,3,*
1
Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Jeollanamdo, Korea
2
Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Jeollanamdo, Korea
3
BK21 Plus Center for Creative Biomedical Scientists, Chonnam National University, Gwangju 61469, Korea
4
BioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Korea
5
Health and Environment Research Institute of Gwangju, 584, Mujin-daero, Seo-gu, Gwangju 61954, Korea
6
Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Jeollanamdo, Korea
7
Department of Cardiology, Chonnam National University Hospital, Gwangju 61469, Korea
8
College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Ryuji Okamoto
Int. J. Mol. Sci. 2021, 22(18), 9944; https://doi.org/10.3390/ijms22189944
Received: 9 August 2021 / Revised: 31 August 2021 / Accepted: 10 September 2021 / Published: 14 September 2021
(This article belongs to the Special Issue Review of Cardiac Fibrosis: Recent Advances and Future Directions)
Various heart diseases cause cardiac remodeling, which in turn leads to ineffective contraction. Although it is an adaptive response to injury, cardiac fibrosis contributes to this remodeling, for which the reactivation of quiescent myofibroblasts is a key feature. In the present study, we investigated the role of the p300/CBP-associated factor (PCAF), a histone acetyltransferase, in the activation of cardiac fibroblasts. An intraperitoneal (i.p.) injection of a high dose (160 mg/kg) of isoproterenol (ISP) induced cardiac fibrosis and reduced the amount of the PCAF in cardiac fibroblasts in the mouse heart. However, the PCAF activity was significantly increased in cardiac fibroblasts, but not in cardiomyocytes, obtained from ISP-administered mice. An in vitro study using human cardiac fibroblast cells recapitulated the in vivo results; an treatment with transforming growth factor-β1 (TGF-β1) reduced the PCAF, whereas it activated the PCAF in the fibroblasts. PCAF siRNA attenuated the TGF-β1-induced increase in and translocation of fibrosis marker proteins. PCAF siRNA blocked TGF-β1-mediated gel contraction and cell migration. The PCAF directly interacted with and acetylated mothers against decapentaplegic homolog 2 (SMAD2). PCAF siRNA prevented TGF-β1-induced phosphorylation and the nuclear localization of SMAD2. These results suggest that the increase in PCAF activity during cardiac fibrosis may participate in SMAD2 acetylation and thereby in its activation. View Full-Text
Keywords: cardiac fibrosis; cardiac fibroblasts; P300/CBP-associated factor; transforming growth factor-β1, acetylation; posttranslational modification cardiac fibrosis; cardiac fibroblasts; P300/CBP-associated factor; transforming growth factor-β1, acetylation; posttranslational modification
Show Figures

Figure 1

MDPI and ACS Style

Lim, Y.; Jeong, A.; Kwon, D.-H.; Lee, Y.-U.; Kim, Y.-K.; Ahn, Y.; Kook, T.; Park, W.-J.; Kook, H. P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation. Int. J. Mol. Sci. 2021, 22, 9944. https://doi.org/10.3390/ijms22189944

AMA Style

Lim Y, Jeong A, Kwon D-H, Lee Y-U, Kim Y-K, Ahn Y, Kook T, Park W-J, Kook H. P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation. International Journal of Molecular Sciences. 2021; 22(18):9944. https://doi.org/10.3390/ijms22189944

Chicago/Turabian Style

Lim, Yongwoon, Anna Jeong, Duk-Hwa Kwon, Yeong-Un Lee, Young-Kook Kim, Youngkeun Ahn, Taewon Kook, Woo-Jin Park, and Hyun Kook. 2021. "P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation" International Journal of Molecular Sciences 22, no. 18: 9944. https://doi.org/10.3390/ijms22189944

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop