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The development of endometrial hyperplasia in aged PD-1-deficient female mice.

Guo G, Li H, Cao D, Chen Y - Diagn Pathol (2014)

Bottom Line: Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively.Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. yongwench@163.com.

ABSTRACT

Background: Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different types of autoimmune diseases depending on the mouse strain but its role in uterus development has not been reported.

Methods: In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a 129svEv-Brd background was analyzed by immunohistochemistry and the uterine morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin staining.

Results: The aged PD-1-/- female mice in a 129svEv-Brd rather than Balb/c background develop endometrial hyperplasia. H&E staining showed an increase in the number of glands, neovascularization and an extremely large luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the expression of PD-1 was observed in glandular/luminal epithelium and cells infiltrating the stroma. Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.

Conclusions: These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.

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The characteristic and anatomic distribution of VEGF in uteri from 2-year old WT and PD-1-/- mice. Immunohistochemistry detection showed (A) no mouse positive staining using IgG isotype control antibodies; (B) the VEGF-positive cells were weakly observed in the glandular/luminal epithelium of WT uteri; (C) Strong VEGF-positive staining was observed in the glandular/luminal epithelium from PD-1-/- uteri. ▲ indicates the glandular epithelium; *indicates the luminal cavity and arrows showed the positive cells; (D) immunofluorescent double staining showed that VEGF is expressed on CD3+ T cells, CD56+ NK cells, CK-18+ epithelial cells, CD68+ macrophages and PD-1+ cells. The blue color indicates nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI), and arrows showed the positive cells. Scale bar = 20 μm. N = 4 of each group.
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Figure 5: The characteristic and anatomic distribution of VEGF in uteri from 2-year old WT and PD-1-/- mice. Immunohistochemistry detection showed (A) no mouse positive staining using IgG isotype control antibodies; (B) the VEGF-positive cells were weakly observed in the glandular/luminal epithelium of WT uteri; (C) Strong VEGF-positive staining was observed in the glandular/luminal epithelium from PD-1-/- uteri. ▲ indicates the glandular epithelium; *indicates the luminal cavity and arrows showed the positive cells; (D) immunofluorescent double staining showed that VEGF is expressed on CD3+ T cells, CD56+ NK cells, CK-18+ epithelial cells, CD68+ macrophages and PD-1+ cells. The blue color indicates nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI), and arrows showed the positive cells. Scale bar = 20 μm. N = 4 of each group.

Mentions: To analyze the potential molecular mechanism for epithelial cell proliferation in aged PD-1-/- uteri, the expression of VEGF, a growth factor essential for cell proliferation and uterine growth, was compared between uteri from PD-1-/- and WT mice in 2 years old. Immunohistochemistry showed that the expression of VEGF was slightly detected in uteri from WT mice (Figure 5B). However, strong VEGF expression was observed in uteri from aged PD-1-/- female mice, and the expression was primarily observed in the luminal epithelium and cells infiltrated in stroma (Figure 5C). Immunofluorescent labeling showed that VEGF was co-expressed with PD-1+ cells, in addition to it expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells (Figure 5D). These results suggest that PD-1 deficiency likely stimulates luminal epithelial cell proliferation through induced VEGF secretion.


The development of endometrial hyperplasia in aged PD-1-deficient female mice.

Guo G, Li H, Cao D, Chen Y - Diagn Pathol (2014)

The characteristic and anatomic distribution of VEGF in uteri from 2-year old WT and PD-1-/- mice. Immunohistochemistry detection showed (A) no mouse positive staining using IgG isotype control antibodies; (B) the VEGF-positive cells were weakly observed in the glandular/luminal epithelium of WT uteri; (C) Strong VEGF-positive staining was observed in the glandular/luminal epithelium from PD-1-/- uteri. ▲ indicates the glandular epithelium; *indicates the luminal cavity and arrows showed the positive cells; (D) immunofluorescent double staining showed that VEGF is expressed on CD3+ T cells, CD56+ NK cells, CK-18+ epithelial cells, CD68+ macrophages and PD-1+ cells. The blue color indicates nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI), and arrows showed the positive cells. Scale bar = 20 μm. N = 4 of each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4066824&req=5

Figure 5: The characteristic and anatomic distribution of VEGF in uteri from 2-year old WT and PD-1-/- mice. Immunohistochemistry detection showed (A) no mouse positive staining using IgG isotype control antibodies; (B) the VEGF-positive cells were weakly observed in the glandular/luminal epithelium of WT uteri; (C) Strong VEGF-positive staining was observed in the glandular/luminal epithelium from PD-1-/- uteri. ▲ indicates the glandular epithelium; *indicates the luminal cavity and arrows showed the positive cells; (D) immunofluorescent double staining showed that VEGF is expressed on CD3+ T cells, CD56+ NK cells, CK-18+ epithelial cells, CD68+ macrophages and PD-1+ cells. The blue color indicates nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI), and arrows showed the positive cells. Scale bar = 20 μm. N = 4 of each group.
Mentions: To analyze the potential molecular mechanism for epithelial cell proliferation in aged PD-1-/- uteri, the expression of VEGF, a growth factor essential for cell proliferation and uterine growth, was compared between uteri from PD-1-/- and WT mice in 2 years old. Immunohistochemistry showed that the expression of VEGF was slightly detected in uteri from WT mice (Figure 5B). However, strong VEGF expression was observed in uteri from aged PD-1-/- female mice, and the expression was primarily observed in the luminal epithelium and cells infiltrated in stroma (Figure 5C). Immunofluorescent labeling showed that VEGF was co-expressed with PD-1+ cells, in addition to it expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells (Figure 5D). These results suggest that PD-1 deficiency likely stimulates luminal epithelial cell proliferation through induced VEGF secretion.

Bottom Line: Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively.Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. yongwench@163.com.

ABSTRACT

Background: Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different types of autoimmune diseases depending on the mouse strain but its role in uterus development has not been reported.

Methods: In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a 129svEv-Brd background was analyzed by immunohistochemistry and the uterine morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin staining.

Results: The aged PD-1-/- female mice in a 129svEv-Brd rather than Balb/c background develop endometrial hyperplasia. H&E staining showed an increase in the number of glands, neovascularization and an extremely large luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the expression of PD-1 was observed in glandular/luminal epithelium and cells infiltrating the stroma. Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.

Conclusions: These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.

Show MeSH
Related in: MedlinePlus