Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration - PubMed (original) (raw)
. 2014 Jul 15;307(2):G196-204.
doi: 10.1152/ajpgi.00077.2014. Epub 2014 May 29.
Affiliations
- PMID: 24875096
- DOI: 10.1152/ajpgi.00077.2014
Free article
Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration
James L Grijalva et al. Am J Physiol Gastrointest Liver Physiol. 2014.
Free article
Abstract
The Hippo signaling pathway has been implicated in mammalian organ size regulation and tumor suppression. Specifically, the Hippo pathway plays a critical role regulating the activity of transcriptional coactivator Yes-associated protein (YAP), which modulates a proliferative transcriptional program. Recent investigations have demonstrated that while this pathway is activated in quiescent livers, its inhibition leads to liver overgrowth and tumorigenesis. However, the role of the Hippo pathway during the natural process of liver regeneration remains unknown. Here we investigated alterations in the Hippo signaling pathway and YAP activation during liver regeneration using a 70% partial hepatectomy (PH) rat model. Our results indicate an increase in YAP activation by 1 day following PH as demonstrated by increased YAP nuclear localization and increased YAP target gene expression. Investigation of the Hippo pathway revealed a decrease in the activation of core kinases Mst1/2 by 1 day as well as Lats1/2 and its adapter protein Mob1 by 3 days following PH. Evaluation of liver-to-body weight ratios indicated that the liver reaches its near normal size by 7 days following PH, which correlated with a return to baseline YAP nuclear levels and target gene expression. Additionally, when liver size was restored, Mst1/2 kinase activation returned to levels observed in quiescent livers indicating reactivation of the Hippo signaling pathway. These findings illustrate the dynamic changes in the Hippo signaling pathway and YAP activation during liver regeneration, which stabilize when the liver-to-body weight ratio reaches homeostatic levels.
Keywords: Hippo signaling pathway; YAP; liver; partial hepatectomy; regeneration.
Copyright © 2014 the American Physiological Society.
Similar articles
- Impaired liver regeneration in aged mice can be rescued by silencing Hippo core kinases MST1 and MST2.
Loforese G, Malinka T, Keogh A, Baier F, Simillion C, Montani M, Halazonetis TD, Candinas D, Stroka D. Loforese G, et al. EMBO Mol Med. 2017 Jan;9(1):46-60. doi: 10.15252/emmm.201506089. EMBO Mol Med. 2017. PMID: 27940445 Free PMC article. - The Hippo signaling pathway in liver regeneration and tumorigenesis.
Hong L, Cai Y, Jiang M, Zhou D, Chen L. Hong L, et al. Acta Biochim Biophys Sin (Shanghai). 2015 Jan;47(1):46-52. doi: 10.1093/abbs/gmu106. Epub 2014 Dec 4. Acta Biochim Biophys Sin (Shanghai). 2015. PMID: 25476204 Review. - The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.
Chen M, Zhang H, Shi Z, Li Y, Zhang X, Gao Z, Zhou L, Ma J, Xu Q, Guan J, Cheng Y, Jiao S, Zhou Z. Chen M, et al. J Biol Chem. 2018 Sep 14;293(37):14455-14469. doi: 10.1074/jbc.RA118.003279. Epub 2018 Aug 2. J Biol Chem. 2018. PMID: 30072378 Free PMC article. - Angiomotins stimulate LATS kinase autophosphorylation and act as scaffolds that promote Hippo signaling.
Mana-Capelli S, McCollum D. Mana-Capelli S, et al. J Biol Chem. 2018 Nov 23;293(47):18230-18241. doi: 10.1074/jbc.RA118.004187. Epub 2018 Sep 28. J Biol Chem. 2018. PMID: 30266805 Free PMC article. - The regulation and function of YAP transcription co-activator.
Zhu C, Li L, Zhao B. Zhu C, et al. Acta Biochim Biophys Sin (Shanghai). 2015 Jan;47(1):16-28. doi: 10.1093/abbs/gmu110. Epub 2014 Dec 8. Acta Biochim Biophys Sin (Shanghai). 2015. PMID: 25487920 Review.
Cited by
- [Inhibiting Yes-associated protein alleviates CCl4 liver fibrosis in mice by reducing epithelial mesenchymal transition].
Zhao W, Ruan H, Wang S, Cheng Y, Lei M, Zhao J, Liu C. Zhao W, et al. Nan Fang Yi Ke Da Xue Xue Bao. 2024 Oct 20;44(10):1839-1849. doi: 10.12122/j.issn.1673-4254.2024.10.01. Nan Fang Yi Ke Da Xue Xue Bao. 2024. PMID: 39523083 Free PMC article. Chinese. - ALKBH5 Protects Against Hepatic Ischemia-Reperfusion Injury by Regulating YTHDF1-Mediated YAP Expression.
Wang P, Xiang M, Zhu L, Zhang R, Zheng X, Zheng Z, Li K. Wang P, et al. Int J Mol Sci. 2024 Oct 27;25(21):11537. doi: 10.3390/ijms252111537. Int J Mol Sci. 2024. PMID: 39519091 Free PMC article. - Sex hormone receptors, calcium-binding protein and Yap1 signaling regulate sex-dependent liver cell proliferation following partial hepatectomy.
Zhu M, Li Y, Shen Q, Gong Z, Liu D. Zhu M, et al. Dis Model Mech. 2024 Oct 1;17(10):dmm050900. doi: 10.1242/dmm.050900. Epub 2024 Oct 30. Dis Model Mech. 2024. PMID: 39397390 Free PMC article. - Cell competition in primary and metastatic colorectal cancer.
van Luyk ME, Krotenberg Garcia A, Lamprou M, Suijkerbuijk SJE. van Luyk ME, et al. Oncogenesis. 2024 Jul 26;13(1):28. doi: 10.1038/s41389-024-00530-5. Oncogenesis. 2024. PMID: 39060237 Free PMC article. Review. - Fenofibrate-promoted hepatomegaly and liver regeneration are PPAR_α_-dependent and partially related to the YAP pathway.
Fan S, Gao Y, Zhao P, Xie G, Zhou Y, Yang X, Li X, Zhang S, Gonzalez FJ, Qu A, Huang M, Bi H. Fan S, et al. Acta Pharm Sin B. 2024 Jul;14(7):2992-3008. doi: 10.1016/j.apsb.2024.03.030. Epub 2024 Mar 26. Acta Pharm Sin B. 2024. PMID: 39027236 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous