Int J Biol Sci
2023; 19(3):994-1006.
doi:10.7150/ijbs.76214 This issueCite
Research Paper
Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation
Di Huang1*, Dan Zhao1*, Ming Li1*, Si-Yu Chang1, Ya-Dong Xue1, Ning Xu1, Si-Jia Li1, Nan-Nan Tang1, Li-Ling Gong1, Yi-Ning Liu1, Hang Yu1, Qing-Sui Li1, Peng-Yu Li1, Jia-Li Liu1, Hai-Xin Chen1, Ming-Bin Liu1, Wan-Yu Zhang1, Xing-Miao Zhao1, Xian-Zhi Lang1, Zhen-Dong Li1, Yu Liu1, Zhi-Yong Ma1, Jia-Min Li1,2,3, Ning Wang1,2,3✉, Hai Tian4,5✉, Ben-Zhi Cai1,2,3✉
1. Department of Pharmacology at College of Pharmacy, Department of Pharmacy at the Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China. 2. Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin, 150081, China. 3. Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, 150081, China. 4. Department of Cardiovascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. 5. Future Medical laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. *These authors contributed equally to this work.
✉ Corresponding authors: Ning Wang, E-mail: wangninghrbmu.edu.cn; Hai Tian, E-mail: doctor_tianhaicom; Ben-Zhi Cai, E-mail: caibenzhicom.
Citation:
Huang D, Zhao D, Li M, Chang SY, Xue YD, Xu N, Li SJ, Tang NN, Gong LL, Liu YN, Yu H, Li QS, Li PY, Liu JL, Chen HX, Liu MB, Zhang WY, Zhao XM, Lang XZ, Li ZD, Liu Y, Ma ZY, Li JM, Wang N, Tian H, Cai BZ. Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation. Int J Biol Sci 2023; 19(3):994-1006. doi:10.7150/ijbs.76214. https://www.ijbs.com/v19p0994.htm
Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-β1 (TGF-β1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-β1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-β1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.
Huang, D., Zhao, D., Li, M., Chang, S.Y., Xue, Y.D., Xu, N., Li, S.J., Tang, N.N., Gong, L.L., Liu, Y.N., Yu, H., Li, Q.S., Li, P.Y., Liu, J.L., Chen, H.X., Liu, M.B., Zhang, W.Y., Zhao, X.M., Lang, X.Z., Li, Z.D., Liu, Y., Ma, Z.Y., Li, J.M., Wang, N., Tian, H., Cai, B.Z. (2023). Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation. International Journal of Biological Sciences, 19(3), 994-1006. https://doi.org/10.7150/ijbs.76214.
ACS
Huang, D.; Zhao, D.; Li, M.; Chang, S.Y.; Xue, Y.D.; Xu, N.; Li, S.J.; Tang, N.N.; Gong, L.L.; Liu, Y.N.; Yu, H.; Li, Q.S.; Li, P.Y.; Liu, J.L.; Chen, H.X.; Liu, M.B.; Zhang, W.Y.; Zhao, X.M.; Lang, X.Z.; Li, Z.D.; Liu, Y.; Ma, Z.Y.; Li, J.M.; Wang, N.; Tian, H.; Cai, B.Z. Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation. Int. J. Biol. Sci. 2023, 19 (3), 994-1006. DOI: 10.7150/ijbs.76214.
NLM
Huang D, Zhao D, Li M, Chang SY, Xue YD, Xu N, Li SJ, Tang NN, Gong LL, Liu YN, Yu H, Li QS, Li PY, Liu JL, Chen HX, Liu MB, Zhang WY, Zhao XM, Lang XZ, Li ZD, Liu Y, Ma ZY, Li JM, Wang N, Tian H, Cai BZ. Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation. Int J Biol Sci 2023; 19(3):994-1006. doi:10.7150/ijbs.76214. https://www.ijbs.com/v19p0994.htm
CSE
Huang D, Zhao D, Li M, Chang SY, Xue YD, Xu N, Li SJ, Tang NN, Gong LL, Liu YN, Yu H, Li QS, Li PY, Liu JL, Chen HX, Liu MB, Zhang WY, Zhao XM, Lang XZ, Li ZD, Liu Y, Ma ZY, Li JM, Wang N, Tian H, Cai BZ. 2023. Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation. Int J Biol Sci. 19(3):994-1006.
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