Angiotensin-(1–7) and angiotensin II induce the transdifferentiation of human endometrial epithelial cells in vitro

Abstract

Intrauterine adhesions (IUA) may be caused by endometrial stromal cell proliferation, increases in myofibroblasts or increases in extracellular matrix secretion. However, the specific mechanisms underlying the development of IUA have yet to be elucidated. The present study identified that angiotensin (Ang) II is capable of promoting endometrial epithelium cell (EEC) proliferation and the transdifferentiation of EECs into myofibroblasts. Furthermore, the present study found that Ang II increased the expression of the myofibroblast specific protein α-smooth muscle actin (α-SMA), decreased the expression and secretion of E-cadherin, and increased the synthesis of collagen type I (Col I) and fibronectin (FN). However, Ang-(1–7) was observed to inhibit Ang II-induced proliferation and transdifferentiation of EECs, decrease the expression of α-SMA, increase the expression of E-cadherin and decrease the synthesis and secretion of Col I and FN. These findings suggest that Ang-(1–7) is capable of inhibiting the Ang II-induced proliferation and transdifferentiation of human EECs and decreases in Col I and FN secretion. The present study may provide insight into the mechanism underlying endometrial fibrosis.

MicroRNA-29b Inhibits Endometrial Fibrosis by Regulating the Sp1-TGF-β1/Smad-CTGF Axis in a Rat Model

“…19 However, during fibrogenesis, endometrial epithelial cells undergo an EMT-like process when massive ECM generated from stromal cells accumulates in the endometrium, resulting in failure to regenerate functional endometrium. 20 The downregulation of miR29b was inversely correlated with uterine Smad3 levels in the present study, which is consistent with the results of other studies of renal fibrosis. It has been demonstrated that TGF-b1 negatively regulates miR-29b expression via Smad3 interaction with a Smad binding site at its promoter in response to TGFb1.…”

Angiotensin II promotes endometrial cancer cell survival

“…All in all, our present observations, as well as results from previous studies conducted on EC tumour samples, indicate a specific link between angiotensin effectiveness and cell differentiation status (2). Our observations are consistent with data presented by Shan et al, showing that Ang II is capable of promoting endometrial epithelium cell proliferation (6). Similar results on the effect of Ang II on cell proliferation and survival were obtained for breast cancer and prostate cancer (12,13).…”

“…The decreased adhesion was quite surprising, but it may have resulted from acquisition of a strong mesenchymal phenotype, in which cells detaching from the basal membrane do not undergo cell death but survive these stressful conditions. Ang II-induced EMT observed in our study was also described by other research groups (6,30). Shan et al recently showed that Ang II promotes activation of endometrial epithelium cells and significantly decreases the expression of E-cadherin, increasing the expression of SMA (6).…”

“…Ang II-induced EMT observed in our study was also described by other research groups (6,30). Shan et al recently showed that Ang II promotes activation of endometrial epithelium cells and significantly decreases the expression of E-cadherin, increasing the expression of SMA (6). Furthermore, Ang II together with TGF-β1 was shown to play a central role in initiating EMT in in vitro models of metastatic tumour development (6).…”

“…All components of the RAS (angiotensinogen, angiotensin converting enzyme, angiotensin receptors) are expressed in many types of tumours, including endometrial cancer (2,4). Moreover, both angiotensin receptors (AT1 and AT2) are overexpressed in different types of cancers, which confirms the role of local RAS in cancer development and progression (3,(5)(6)(7)(8).…”