Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice

Yi Cheng Chen, Yu Chu Su, Gia Shing Shieh, Bing Hua Su, Wen Cheng Su, Pei Hsin Huang, Si Tse Jiang, Ai Li Shiau, Chao Liang Wu

Research output: Contribution to journalArticle

Abstract

Polycystic kidney disease (PKD) is characterized by the expansion of fluid-filled cysts in the kidney, which impair the function of kidney and eventually leads to end-stage renal failure. It has been previously demonstrated that transgenic overexpression of prothymosin α (ProT) induces the development of PKD; however, the underlying mechanisms remain unclear. In this study, we used a mouse PKD model that sustains kidney-specific low-expression of Pkd1 to illustrate that aberrant up-regulation of ProT occurs in cyst-lining epithelial cells, and we further developed an in vitro cystogenesis model to demonstrate that the suppression of ProT is sufficient to reduce cyst formation. Next, we found that the expression of ProT was accompanied with prominent augmentation of protein acetylation in PKD, which results in the activation of downstream signal transducer and activator of transcription (STAT) 3. The pathologic role of STAT3 in PKD has been previously reported. We determined that this molecular mechanism of protein acetylation is involved with the interaction between ProT and STAT3; consequently, it causes the deprivation of histone deacetylase 3 from the indicated protein. Conclusively, these results elucidate the significant role of ProT, including protein acetylation and STAT3 activation in PKD, which represent potential for ameliorating the disease progression of PKD.—Chen, Y.-C., Su, Y.-C., Shieh, G.-S., Su, B.-H., Su, W.-C., Huang, P.-H., Jiang, S.-T., Shiau, A.-L., Wu, C.-L. Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice. FASEB J. 33, 13051–13061 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)13051-13061
Number of pages11
JournalFASEB Journal
Volume33
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • HDAC3
  • polycystic kidney disease
  • tubulogenesis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Chen, Y. C., Su, Y. C., Shieh, G. S., Su, B. H., Su, W. C., Huang, P. H., Jiang, S. T., Shiau, A. L., & Wu, C. L. (2019). Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice. FASEB Journal, 33(11), 13051-13061. https://doi.org/10.1096/fj.201900504R