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Array profiling reveals contribution of Cthrc1 to growth of the denervated rat urinary bladder

Zhu, Baoyi LU ; Ekman, Mari LU ; Svensson, Daniel LU ; Lindvall, Jessica M; Nilsson, Bengt-Olof LU ; Uvelius, Bengt LU and Swärd, Karl LU (2018) In American Journal of Physiology-Renal Physiology1997-01-01+01:00 314(5). p.893-905
Abstract

Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold, and 2,890 mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with array data from obstructed bladders demonstrated overlap between the conditions, and 10% of mRNAs changed significantly and in the same direction. Many mRNAs, including collagen triple helix repeat... (More)

Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold, and 2,890 mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with array data from obstructed bladders demonstrated overlap between the conditions, and 10% of mRNAs changed significantly and in the same direction. Many mRNAs, including collagen triple helix repeat containing 1 ( Cthrc1), Prc1, Plod2, and Dkk3, and miRNAs, such as miR-212 and miR-29, resided in the shared signature. Discordantly regulated transcripts in the two models were rare, making up for <0.07% of all changes, and the gene products in this category localized to the urothelium of normal bladders. These transcripts may potentially be used to diagnose sensory denervation. Western blotting demonstrated directionally consistent changes at the protein level, with increases of, e.g., Cthrc1, Prc1, Plod2, and Dkk3. We chose Cthrc1 for further studies and found that Cthrc1 was induced in the smooth muscle cell (SMC) layer following denervation. TGF-β1 stimulation and miR-30d-5p inhibition increased Cthrc1 in bladder SMCs, and knockdown and overexpression of Cthrc1 reduced and increased SMC proliferation. This work defines common and distinguishing features of bladder denervation and obstruction and suggests a role for Cthrc1 in bladder growth following denervation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology-Renal Physiology1997-01-01+01:00
volume
314
issue
5
pages
893 - 905
publisher
American Physiological Society
external identifiers
  • scopus:85059885261
ISSN
1522-1466
DOI
10.1152/ajprenal.00499.2017
language
English
LU publication?
yes
id
9c13dad7-ba61-4c05-8de9-68d062c4b557
date added to LUP
2018-08-27 13:56:34
date last changed
2019-02-20 11:24:54
@article{9c13dad7-ba61-4c05-8de9-68d062c4b557,
  abstract     = {<p>Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold, and 2,890 mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with array data from obstructed bladders demonstrated overlap between the conditions, and 10% of mRNAs changed significantly and in the same direction. Many mRNAs, including collagen triple helix repeat containing 1 ( Cthrc1), Prc1, Plod2, and Dkk3, and miRNAs, such as miR-212 and miR-29, resided in the shared signature. Discordantly regulated transcripts in the two models were rare, making up for &lt;0.07% of all changes, and the gene products in this category localized to the urothelium of normal bladders. These transcripts may potentially be used to diagnose sensory denervation. Western blotting demonstrated directionally consistent changes at the protein level, with increases of, e.g., Cthrc1, Prc1, Plod2, and Dkk3. We chose Cthrc1 for further studies and found that Cthrc1 was induced in the smooth muscle cell (SMC) layer following denervation. TGF-β1 stimulation and miR-30d-5p inhibition increased Cthrc1 in bladder SMCs, and knockdown and overexpression of Cthrc1 reduced and increased SMC proliferation. This work defines common and distinguishing features of bladder denervation and obstruction and suggests a role for Cthrc1 in bladder growth following denervation.</p>},
  author       = {Zhu, Baoyi and Ekman, Mari and Svensson, Daniel and Lindvall, Jessica M and Nilsson, Bengt-Olof and Uvelius, Bengt and Swärd, Karl},
  issn         = {1522-1466},
  language     = {eng},
  month        = {05},
  number       = {5},
  pages        = {893--905},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology-Renal Physiology1997-01-01+01:00},
  title        = {Array profiling reveals contribution of Cthrc1 to growth of the denervated rat urinary bladder},
  url          = {http://dx.doi.org/10.1152/ajprenal.00499.2017},
  volume       = {314},
  year         = {2018},
}