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Stem cell antigen/Ly6a protects against bladder fibrosis in mice

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.

Am J Physiol Renal Physiol. 2019 Sep 19; 317(6):F1503-f1512

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.

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