Prostatic E. coli infection drives CCR2-dependent recruitment of fibrocytes and collagen production.

Prostate fibrosis contributes to lower urinary tract dysfunction (LUTD). To develop targeted treatments for prostate fibrosis, it is necessary to identify 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 (E.

A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.

Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins.

Genetic background but not prostatic epithelial beta-catenin influences susceptibility of male mice to testosterone and estradiol-induced urinary dysfunction.

Urinary voiding dysfunction in aging men can cause bothersome symptoms and irreparable tissue damage. Underlying mechanisms are not fully known. We previously demonstrated that subcutaneous, slow-release testosterone and estradiol implants (T+E2) drive a pattern of urinary voiding dysfunction in male mice that resembles that of aging men.

Progenitors in prostate development and disease.

The prostate develops by epithelial budding and branching processes that occur during fetal and postnatal stages. The adult prostate demonstrates remarkable regenerative capacity, with the ability to regrow to its original size over multiple cycles of castration and androgen administration. This capacity for controlled regeneration prompted the search for an androgen-independent epithelial progenitor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa).

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

Background: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors.

Methods: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes.

and lactational 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) exposure exacerbates urinary dysfunction in hormone-treated C57BL/6J mice through a non-malignant mechanism involving proteomic changes in the prostate that differ from those elicited by testosterone and estradiol.

A recent study directed new focus on the fetal and neonatal environment as a risk factor for urinary dysfunction in aging males. Male mice were exposed and via lactation (IUL) to the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) and then administered slow-release, subcutaneous implants of testosterone and estradiol (T+E2) as adults to mimic the hormonal environment of aging men. IUL TCDD exposure worsened T+E2-induced voiding dysfunction.

Lack of discreet colocalization of epithelial apoptosis to the atretic precursor in the colon of the Fibroblast growth factor receptor 2IIIb mouse and staining consistent with cellular movement suggest a revised model of atresia formation.

Background: Colonic atresias in the Fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) mouse model have been attributed to increased epithelial apoptosis and decreased epithelial proliferation at embryonic day (E) 10.5. We therefore hypothesized that these processes would colocalize to the distal colon where atresias occur (atretic precursor) and would be excluded or minimized from the proximal colon and small intestine.

Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation.

We genetically engineered expression of an activated form of P110 alpha, the catalytic subunit of PI3K, in mouse prostate epithelium to create a mouse model of direct PI3K activation (Pbsn-cre4Prb;PI3K ). We hypothesized that direct activation would cause rapid neoplasia and cancer progression. Pbsn-cre4Prb;PI3K mice developed widespread prostate intraepithelial hyperplasia, but stromal invasion was limited and overall progression was slower than anticipated.

A temporal and spatial map of axons in developing mouse prostate.

Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation. Morphogenetic signaling pathways reawakened during disease progression may drive this axon remodeling. These pathways are linked to proliferative activities in prostate cancer and benign prostate hyperplasia.

An immunohistochemical identification key for cell types in adult mouse prostatic and urethral tissue sections.

Though many methods can be used to identify cell types contained in complex tissues, most require cell disaggregation and destroy information about where cells reside in relation to their microenvironment. Here, we describe a polytomous key for cell type identification in intact sections of adult mouse prostate and prostatic urethra. The key is organized as a decision tree and initiates with one round of immunostaining for nerve, epithelial, fibromuscular/hematolymphoid, or vascular associated cells.

Specific renal parenchymal-derived urinary extracellular vesicles identify age-associated structural changes in living donor kidneys.

Non-invasive tests to identify age and early disease-associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age- and sex-stratified living kidney donors before kidney donation.