Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

Abstract

As an analog to the endothelium situated next to the vascular smooth muscle, the epithelium is emerging as an important regulator of smooth muscle contraction in many vital organs/tissues by interacting with other cell types and releasing epithelium-derived factors, among which prostaglandins have been demonstrated to play a versatile role in governing smooth muscle contraction essential to the physiological and pathophysiological processes in a wide range of organ systems. As widely distributed throughout the body, including the blood vessels, airways, gastrointestinal, urinary, and reproductive tracts, smooth muscles have a variety of critical functions such as controlling blood pressure, respiration, and gastrointestinal peristalsis. Abnormality in smooth muscle contractility results in various disorders and diseases including hypertension, asthma, and dyspepsia (89, 95,179). Therefore, smooth muscle contraction is tightly regulated. Apart from the long-recognized regulation by neurotransmitters released from the innervating nerve endings or hormones from the blood stream nearby (66), smooth muscle contraction has been known, for over three decades, to be regulated by the endothelium lining the blood vessels with nitric oxide (NO) as the most important endothelial-derived factor (51, 121). Over recent decades, evidence has also been accumulated indicating an important role of the epithelium, the cell layer lining the luminal surface of many organs or tracts, such as the trachea/bronchus, stomach, intestine, bladder, and reproductive organs, in the regulation of smooth muscle contraction, with a number of epithelium-derived factors identified. However, the importance of the epithelium in regulating smooth muscle tones has not been adequately appreciated. In this review, we will examine the evidence collected from a number of organ systems and hope to provide a clearer picture as to how the epithelium acts as an indispensable regulator of smooth muscle contraction, with epithelium-derived prostaglandins (PGs) as the key mediators, participating in many vital physiological processes as well as the pathogenesis of many diseases.

Regulation of miR-101/miR-199a-3p by the epithelial sodium channel during embryo implantation: involvement of CREB phosphorylation

“…Cyclooxygenase type 2 (COX2), a rate-limiting enzyme for prostaglandins (PGs) production in multiple organs and tissues (Ruan et al 2011), is abundantly expressed in the endometrium during implantation period in mice and humans (Lim et al 1997, Critchley et al 1999, Marions & Danielsson 1999) and known to be a key factor for embryo implantation. COX2-knockout mice show multiple problems in female reproduction, including implantation failure (Lim et al 1997, Matsumoto et al 2002.…”

A sequence of events in the uterus prior to implantation in the mouse

“…The epithelium is considered as an important regulator of smooth muscle contraction, and releasing epithelium-derived factors, particularly prostaglandins are considered to play important role in governing smooth muscle contraction [35]. Thus, the presence of a blastocyst in the luminal epithelial prior to be transported the site of implantation may involve embryonic signal transmission to the underlying luminal epithelial cells and this may be transmitted underneath to the circular smooth muscle layer.…”

Introducing, OncoTarget

“…Also, impaired endometrial PGs synthesis was observed in women with repeatedly implantation failure in IVF trials [7]. Prostaglandin E2 (PGE 2 ), mainly produced by COX-2-driven synthesis, is considered one of the most important PGs to initiate [5,8], an endometrial stromal differentiation process required for embryo implantation [9]. We have previously demonstrated that the epithelial sodium channel (ENaC) in the endometrial epithelial cells can be activated by embryo-derived protease, which subsequently triggers a sequence of events in endometrial epithelial cells, including Ca 2+ increase, phosphorylation of CREB (Ca 2+ / cAMP responsive element binding protein), downregulation of miR101 and miR199a, upregulation of COX-2 and eventually PGE 2 production and release to the stroma, leading to decidualization and embryo implantation [10,11].…”