Ventral prostate fibrosis in the Akita mouse is associated with macrophage and fibrocyte infiltration

Abstract

A higher incidence of lower urinary tract symptoms (LUTS) among diabetic men is unexplained. Recently, prostate inflammation and fibrosis have been implicated as major contributing factors to bladder outlet obstruction and LUTS. We characterized the inflammatory cell infiltrate and collagen content of the anterior, dorsal, and ventral lobes of 18-week-old DBA2J.Ins2-Akita mice (Akita) and age-matched control mice. We performed hematoxylin and eosin staining to score tissue injury and inflammation, picrosirius red staining to quantitate collagen content, and immunostaining to identify monocytes/macrophages and infiltrating fibrocytes. We observed significantly greater numbers of monocytes/macrophages and fibrocytes specifically in the ventral prostate of the Akita mice and found that this was associated with significant greater collagen content specifically in the ventral prostate of the Akita mice. These observations support the inference that diabetes elicits monocyte/macrophage infiltration and collagen accumulation in the prostate and suggest that further study of Akita mice may inform translational studies of diabetes in the genesis prostatic inflammation, prostatic fibrosis, and LUTS.

Figure 1

Representative H&E stained sections of the AP, DLP, and VP of 18-weeks-old DBA2J (WT: n = 4), DBA2J.Ins2-Aktia (diabetic: n = 3), or DBA2J.Ins2-Akita mice with severe inflammation (diabetic: n = 1).

Figure 2

Number of inflammatory cells in the AP, DLP, and VP of 18-week-old DBA2J (WT, white circles), DBA2J.Ins2-Akita (diabetic, white squares), or DBA2J.Ins2-Akita with severe inflammation (diabetic, black squares) by H&E staining and IHC presented as the mean number of cells. (a) Neutrophils, (b) monocytes/macrophages, (c) T lymphocytes, and (d) B lymphocytes. *P value <0.05.

Figure 3

Representative section of the AP, DLP, and VP of 18-week-old DBA2J (WT; (a), (d), and (g)), DBA2J.Ins2-Akita (diabetic; (b), (e), and (h)), or DBA2J.Ins2-Akita with severe inflammation (diabetic; (c), (f), and (i)) stained for collagen with picrosirius red. Quantification results of collagen level in (a)~(i) ((j), white circles = WT, white squares = Akita, and black squares = Akita with severe inflammation). *P value <0.05.

Figure 4

Representative section of the VP of 18-week-old DBA2J (WT; (a)), DBA2J.Ins2-Akita (diabetic; (b), (d)), or DBA2J.Ins2-Akita with severe inflammation (diabetic; (c), (e)) stained for CD45 and vimentin. Quantification results of fibrocyte infiltration in the AP, DLP (image not shown), and VP ((f), white circles = WT, white squares = Akita, and black squares = Akita with severe inflammation). *P value <0.05. Arrow denotes CD45+/vimentin+ fibrocytes.