Abstract
Keratinocyte growth factor (KGF) functions in epithelial growth and differentiation in many tissues and organs. KGF is expressed in the uterine endometrial epithelial cells during the estrous cycle and pregnancy in pigs, and receptors for KGF (KGFR) are expressed by conceptus trophectoderm and endometrial epithelia. KGF has been shown to stimulate the proliferation and differentiation of conceptus trophectoderm. However, the role of KGF on the endometrial epithelial cells has not been determined. Therefore, this study determined the effect of KGF on proliferation and differentiation of endometrial epithelial cells in vitro and in vivo using an immortalized porcine luminal epithelial (pLE) cell line and KGF infusion into the uterine lumen of pigs between Days 9 and 12 of estrous cycle. Results showed that KGF did not stimulate proliferation of uterine endometrial epithelial cells in vitro and in vivo determined by the [ 3 H]thymidine incorporation assay and the proliferating cell nuclear antigen staining, respectively. Effects of KGF on expression of several markers for epithelial cell differentiation, including integrin receptor subunits a4, a5 and β1, plasmin/trypsin inhibitor, uteroferrin and retinol-binding protein were determined by RT-PCR, Northern and slot blot analyses, and immunohistochemisty, and KGF did not affect epithelial cell differentiation in vitro and in vivo. These results show that KGF does not induce epithelial cell proliferation and differentiation, suggesting that KGF produced by endometrial epithelial cells acts on conceptus trophectoderm in a paracrine manner rather than on endometrial epithelial cells in an autocrine manner.
Highlights
Effects of Keratinocyte growth factor (KGF) on expression of several markers for epithelial cell differentiation, including integrin receptor subunits α4, α5 and β1, plasmin/trypsin inhibitor, uteroferrin and retinol-binding protein were determined by RT-PCR, Northern and slot blot analyses, and immunohistochemisty, and KGF did not affect epithelial cell differentiation in vitro and in vivo. These results show that KGF does not induce epithelial cell proliferation and differentiation, suggesting that KGF produced by endometrial epithelial cells acts on conceptus trophectoderm in a paracrine manner rather than on endometrial epithelial cells in an autocrine manner
Secretory products include transport proteins (Roberts and Bazer, 1988; Harney et al, 1993), enzymes (Fazleabas et al, 1983), extracellular matrix proteins (Garlow et al, 2002) and growth factors (Simmen et al, 1990; Ka et al, 2000). Among those secretory proteins KGF is produced by the uterine endometrium during pregnancy and diestrus of the estrous cycle with a unique cell-type specific expression (Ka et al, 2000)
The known functions of KGF in many cells and tissues and the pattern of KGF and KGFR expression in the porcine uterus (Ka et al, 2000) made us to hypothesize that KGF of endometrial origin acts on the proliferation and differentiation of conceptus trophectoderm and differentiation of uterine endometrial epithelial cells
Summary
The uterus provides an environment that supports KGF gene expression is up-regulated by various factors, embryonic development by synthesizing and secreting a including steroid hormones, cytokines and other growth variety of products, termed histotroph (Roberts and Bazer, factors (Rubin et al, 1995). Expression of KGF in the porcine uterine (Ka et al, 2001), it is not expected that KGF affects endometrium is up-regulated by estrogens (E2), which is endometrial epithelial cell proliferation, but it may affect the maternal recognition signal in pigs (Bazer et al, 1989), uterine epithelial cell differentiation. During early and KGF functions in proliferation and differentiation of pregnancy, uterine endometrial epithelial cells undergo conceptus trophectoderm (Ka et al, 2001). These findings differentiation to increase uterine receptivity to implanting suggested that in the pig, which is the only species blastocysts (Burghardt et al, 1998).
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