Stem cell antigen/Ly6a protects against bladder fibrosis in mice

Nicholas M. Tassone, Belinda Li, Mehul S. Patel, Megan Y. Devine, Paula R. Firmiss, Andrew D. Gould, Kirsten S. Kochan, Reid A. Stubbee, Diana K. Bowen, Robert W. Dettman, Edward M. Gong*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We have defined a population of stem cell antigen (Sca)-1+/CD34+/lin- mesenchymal stem cells in the mouse urinary bladder. These cells are reduced after partial bladder outlet obstruction (PO). To test the role of Sca-1 expressed by these cells, we analyzed bladders from Sca-1 knockout (KO) mice in both uninjured male mice and male mice subjected to PO. We found that loss of Sca-1 alone had little effect on bladder development or function but reduced the total number of mesenchymal stem cells by 30%. After PO, bladders from Sca-1-null KO male mice were larger, with more collagen and less muscle, than obstructed wild-type mice. Steady-state levels of caldesmon were significantly reduced and levels of fibroblast-specific protein 1 were significantly increased in Sca-1 KO mice compared with wild-type mice after PO. In investigating the effects of PO on cell proliferation, we found that loss of Sca-1 changed the timing of cell division in CD34+/lin-, collagen-producing, and smooth muscle cells. PO in combination with loss of Sca-1 drastically reduced the ability of CD34+/lin- cells to form colonies in vitro. Our findings therefore support the hypothesis that Sca-1 protects the bladder from fibrotic remodeling after obstruction, in part by influencing the proliferation of cells responding to the injury.

Original languageEnglish (US)
Pages (from-to)F1503-F1512
JournalAmerican Journal of Physiology - Renal Physiology
Volume317
Issue number6
DOIs
StatePublished - 2019

Keywords

  • Bladder outlet obstruction
  • Fibrosis
  • Obstructive uropathy
  • Stem cell antigen-1

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'Stem cell antigen/Ly6a protects against bladder fibrosis in mice'. Together they form a unique fingerprint.

  • Cite this

    Tassone, N. M., Li, B., Patel, M. S., Devine, M. Y., Firmiss, P. R., Gould, A. D., Kochan, K. S., Stubbee, R. A., Bowen, D. K., Dettman, R. W., & Gong, E. M. (2019). Stem cell antigen/Ly6a protects against bladder fibrosis in mice. American Journal of Physiology - Renal Physiology, 317(6), F1503-F1512. https://doi.org/10.1152/ajprenal.00160.2019