Scharpf Brandon R, Ruetten Hannah, Sandhu Jaskiran, Wegner Kyle A, Chandrashekar Sneha, Fox Olivia, Turco Anne E, Cole Clara, Arendt Lisa M, Strand Douglas W, Vezina Chad M
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
George M. O'Brien Center for Benign Urologic Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dis Model Mech. 2025 Jan 1;18(1). doi: 10.1242/dmm.052012. Epub 2025 Jan 24.
Prostate fibrosis contributes to lower urinary tract dysfunction (LUTD). To develop targeted treatments for prostate fibrosis, it is necessary to identify the cell types and molecular pathways required for collagen production. We used a genetic approach to label and track potential collagen-producing cell lineages in mouse prostate through a round of Escherichia coli UTI89-mediated prostate inflammation. E. coli increased collagen density and production in Gli1+, S100a4+, Lyz2+ and Cd2+ cell lineages, but not in Myh11+ or Srd5a2+ cell lineages, in the mouse prostate. Molecular phenotyping revealed GLI1+LYZ+S100A4+ cells (fibrocytes) in histologically inflamed human prostate. These fibrocytes colocalized with regions of increased collagen in men with LUTD. Fibrocyte recruitment and collagen synthesis was impaired in Ccr2 null mice but restored by allotransplantation of Rosa-GFP donor bone marrow-derived cells. These results suggest that bone marrow-derived fibrocytes are a mediator of prostatic collagen accumulation.
前列腺纤维化会导致下尿路功能障碍（LUTD）。为了开发针对前列腺纤维化的靶向治疗方法，有必要确定胶原蛋白产生所需的细胞类型和分子途径。我们采用了一种基因方法，通过一轮大肠杆菌UTI89介导的前列腺炎症来标记和追踪小鼠前列腺中潜在的胶原蛋白产生细胞谱系。大肠杆菌增加了小鼠前列腺中Gli1 +、S100a4 +、Lyz2 +和Cd2 +细胞谱系中的胶原蛋白密度和产生，但在Myh11 +或Srd5a2 +细胞谱系中没有增加。分子表型分析揭示了组织学上发炎的人类前列腺中的GLI1 + LYZ + S100A4 +细胞（纤维细胞）。这些纤维细胞与LUTD男性中胶原蛋白增加的区域共定位。在Ccr2基因敲除小鼠中，纤维细胞募集和胶原蛋白合成受损，但通过Rosa-GFP供体骨髓来源细胞的同种异体移植得以恢复。这些结果表明，骨髓来源的纤维细胞是前列腺胶原蛋白积累的介质。
