This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research Article
Kojiro Nagai
Institute of Biomedical Sciences, Tokushima University Graduate School
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
p16 is an inhibitor of cyclin-dependent kinases and regulating senescence-mediated arrest as well as p21. The expression of p16 has been evaluated in human kidney diseases. However, the regulation of p16 nuclear translocation has yet to be fully investigated. TGF-β1 is well-known to be one of the major cytokines in developing kidney diseases. TGF-β1 can upregulate p21 expression and be involved in the process of senescence. In contrast, the relationship between TGF-β1 and p16 has been poorly investigated. Here, we report the role of TGF-β1-Smad3 pathway to regulate the p16 behavior in glomerular endothelial cells. To clarify the role of TGF-β1 in the regulation of p16, we analyzed podocyte-specific TGF-β1 overexpression mice. In glomeruli, p16 was found in the nuclei of glomerular endothelial cells, leading to endothelial cellular senescence. However, the expression level of p16 was not increased in glomeruli. In cultured endothelial cells, TGF-β1 induced nuclear translocation of p16 without the increase in p16 expression. Among human glomerular diseases, p16 was detected in the nuclei of endothelial cells. In summary, we could show the novel role of podocyte TGF-β1 in the management of p16 behavior and cellular senescence in glomeruli, which has clinical relevance for human glomerular diseases.
Keywords
cells, human, kidney, diseases, nuclear translocation, cellular senescence,
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryInformation.pdf
Supplementary Fig. S1
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 03 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 08 Jul, 2021
Reviews received
Received 24 Jun, 2021
Reviewers agreed
On 13 Jun, 2021
Reviewers invited
Invitations sent on 12 Jun, 2021
Editor assigned
On 07 Jun, 2021
Editor invited
On 01 Jun, 2021
Submission checks complete
On 31 May, 2021
First submitted
On 26 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Kojiro Nagai
Institute of Biomedical Sciences, Tokushima University Graduate School
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 03 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 08 Jul, 2021
Reviews received
Received 24 Jun, 2021
Reviewers agreed
On 13 Jun, 2021
Reviewers invited
Invitations sent on 12 Jun, 2021
Editor assigned
On 07 Jun, 2021
Editor invited
On 01 Jun, 2021
Submission checks complete
On 31 May, 2021
First submitted
On 26 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
p16 is an inhibitor of cyclin-dependent kinases and regulating senescence-mediated arrest as well as p21. The expression of p16 has been evaluated in human kidney diseases. However, the regulation of p16 nuclear translocation has yet to be fully investigated. TGF-β1 is well-known to be one of the major cytokines in developing kidney diseases. TGF-β1 can upregulate p21 expression and be involved in the process of senescence. In contrast, the relationship between TGF-β1 and p16 has been poorly investigated. Here, we report the role of TGF-β1-Smad3 pathway to regulate the p16 behavior in glomerular endothelial cells. To clarify the role of TGF-β1 in the regulation of p16, we analyzed podocyte-specific TGF-β1 overexpression mice. In glomeruli, p16 was found in the nuclei of glomerular endothelial cells, leading to endothelial cellular senescence. However, the expression level of p16 was not increased in glomeruli. In cultured endothelial cells, TGF-β1 induced nuclear translocation of p16 without the increase in p16 expression. Among human glomerular diseases, p16 was detected in the nuclei of endothelial cells. In summary, we could show the novel role of podocyte TGF-β1 in the management of p16 behavior and cellular senescence in glomeruli, which has clinical relevance for human glomerular diseases.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryInformation.pdf
Supplementary Fig. S1
Loading...