Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Journal Volume
33
Journal Issue
11
Pages
13051-13061
Date Issued
2019
Author(s)
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. ? FASEB
Subjects
HDAC3; polycystic kidney disease; tubulogenesis
SDGs
Other Subjects
histone deacetylase 3; lentivirus vector; prothymosin alpha; short hairpin RNA; STAT3 protein; polycystic kidney disease 1 protein; polycystin; protein precursor; prothymosin alpha; STAT3 protein; Stat3 protein, mouse; thymosin; animal cell; animal experiment; animal model; animal tissue; Article; autosomal dominant disorder; controlled study; disease course; end stage renal disease; HEK293T cell line; human; human cell; immunoblotting; kidney polycystic disease; kidney tubule; MDCK cell line; mouse; nonhuman; priority journal; protein acetylation; protein deficiency; protein expression; tissue specificity; acetylation; animal; disease exacerbation; dog; genetics; HEK293 cell line; kidney polycystic disease; knockout mouse; metabolism; pathology; physiology; Acetylation; Animals; Disease Progression; Dogs; HEK293 Cells; Humans; Madin Darby Canine Kidney Cells; Mice; Mice, Knockout; Polycystic Kidney Diseases; Protein Precursors; STAT3 Transcription Factor; Thymosin; TRPP Cation Channels
Publisher
NLM (Medline)
Type
journal article