Ablating Lgr5-expressing prostatic stromal cells activates the ERK-mediated mechanosensory signaling and disrupts prostate tissue homeostasis.
Ablating Lgr5-expressing prostatic stromal cells activates the ERK-mediated mechanosensory signaling and disrupts prostate tissue homeostasis.
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DOI：
10.1016/j.celrep.2022.111313
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发表时间：
2022-09-06
期刊：
影响因子：
8.8
通讯作者：
Xin, Li
中科院分区：
文献类型：
--
作者：
Wei, Xing;Zhang, Li;Zhang, Yiqun;Cooper, Cody;Brewer, Chris;Tsai, Chia-Feng;Wang, Yi-Ting;Glaz, Micah;Wessells, Hunter B.;Que, Jianwe;Titus, Mark A.;Cirulli, Vincenzino;Glaser, Adam;Liu, Tao;Reder, Nicholas P.;Creighton, Chad J.;Xin, Li
Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5+ stromal cells. RNA sequencing (RNA-seq) analysis indicates that ablating the Lgr5+ stromal cells activates a mechanosensory response. Ablating the Lgr5+ stromal cells impairs the control of prostatic ductal outlet, increases prostate tissue stiffness, and activates the mitogen-activated protein kinase (MAPK). Suppressing MAPK overrides the elevated epithelial proliferation. In summary, the Lgr5+ stromal cells regulate prostate tissue homeostasis and maintain its functional integrity in a long-distance manner. Our study implies that the cells at organ junctions most likely control organ homeostasis by sustaining a balanced mechanoforce. Wei et al. show that the stromal cells at the junction of mouse prostate and urethra highly express Lgr5. Genetically ablating these cells impairs the control of prostatic ductal outlet, increases prostate tissue stiffness, activates the mitogen-activated protein kinase (MAPK)-mediated mechanosensory response, and rapidly induces prostate epithelial turnover and dedifferentiation.
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DOI：
10.1002/path.5751
发表时间：
2021-10
期刊：
The Journal of pathology
影响因子：
--
作者：
Joseph DB;Henry GH;Malewska A;Reese JC;Mauck RJ;Gahan JC;Hutchinson RC;Malladi VS;Roehrborn CG;Vezina CM;Strand DW
通讯作者：
Strand DW
影响因子：
120.7
作者：
Leitzmann, MF;Platz, EA;Giovannucci, E
通讯作者：
Giovannucci, E
影响因子：
7.7
作者：
Fernández, L;Galán, Y;González, C
通讯作者：
González, C
影响因子：
64.5
作者：
Gur C;Wang SY;Sheban F;Zada M;Li B;Kharouf F;Peleg H;Aamar S;Yalin A;Kirschenbaum D;Braun-Moscovici Y;Jaitin DA;Meir-Salame T;Hagai E;Kragesteen BK;Avni B;Grisariu S;Bornstein C;Shlomi-Loubaton S;David E;Shreberk-Hassidim R;Molho-Pessach V;Amar D;Tzur T;Kuint R;Gross M;Barboy O;Moshe A;Fellus-Alyagor L;Hirsch D;Addadi Y;Erenfeld S;Biton M;Tzemach T;Elazary A;Naparstek Y;Tzemach R;Weiner A;Giladi A;Balbir-Gurman A;Amit I
通讯作者：
Amit I
影响因子：
50.3
作者：
Choi N;Zhang B;Zhang L;Ittmann M;Xin L
通讯作者：
Xin L