| First Author | Lin L | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 320 |
| Issue | 4 | Pages | H1634-H1645 |
| PubMed ID | 33635162 | Mgi Jnum | J:305040 |
| Mgi Id | MGI:6514251 | Doi | 10.1152/ajpheart.00538.2020 |
| Citation | Lin L, et al. (2021) Pygo1 regulates pathological cardiac hypertrophy via a beta-catenin-dependent mechanism. Am J Physiol Heart Circ Physiol 320(4) |
| abstractText | Wnt/beta-catenin signalling plays a key role in pathological cardiac remodelling in adults. The identification of a tissue-specific Wnt/beta-catenin interaction factor may realise a tissue-specific clinical targeting strategy. Drosophila Pygo codes for the core interaction factor of Wnt/beta-catenin. Two Pygo homologs, Pygo1 and Pygo2, have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease remains unelucidated. Here, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios and increased cell size. The canonical beta-catenin/T-cell transcription factor 4 complex was abundant in Pygo1-overexpressingtransgenic(Pygo1-TG) cardiac tissue,and the downstream genes of Wnt signaling, i.e., Axin2, Ephb3, and C-myc, were upregulated. A tail vein injection of beta-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodelling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/beta-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway. |
