TY - JOUR
T1 - Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1-deficient mice
AU - Chen, Yi Cheng
AU - Su, Yu Chu
AU - Shieh, Gia Shing
AU - Su, Bing Hua
AU - Su, Wen Cheng
AU - Huang, Pei Hsin
AU - Jiang, Si Tse
AU - Shiau, Ai Li
AU - Wu, Chao Liang
N1 - Funding Information:
The authors are grateful to Dr. A. B. Vartapetian (Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia) for generously providing the anti-ProT mAb (clone 2F11). The RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center (Academia Sinica, Taipei, Taiwan). This work was supported by grants from the Ministry of Science and Technology (MOST) (103-2320-B-006-047-MY3 and 105-2320-B-006-038-MY3). The authors declare no conflicts of interest.
Funding Information:
The authors are grateful to Dr. A. B. Vartapetian (Belozersky Institute of Physico‐Chemical Biology, Moscow State University, Moscow, Russia) for generously providing the anti‐ProT mAb (clone 2F11). The RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center (Academia Sinica, Taipei, Taiwan). This work was supported by grants from the Ministry of Science and Technology (MOST) (103‐2320‐B‐006‐047‐MY3 and 105‐2320‐B‐006‐038‐MY3). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074379742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074379742&partnerID=8YFLogxK
U2 - 10.1096/fj.201900504R
DO - 10.1096/fj.201900504R
M3 - Article
C2 - 31589480
AN - SCOPUS:85074379742
SN - 0892-6638
VL - 33
SP - 13051
EP - 13061
JO - FASEB Journal
JF - FASEB Journal
IS - 11
ER -