Diverse properties of the mesothelial cells in health and disease

Abstract

Mesothelial cells (MCs) form the superficial anatomic layer of serosal membranes, including pleura, pericardium, peritoneum, and the tunica of the reproductive organs. MCs produce a protective, non-adhesive barrier against physical and biochemical damages. MCs express a wide range of phenotypic markers, including vimentin and cytokeratins. MCs play key roles in fluid transport and inflammation, as reflected by the modulation of biochemical markers such as transporters, adhesion molecules, cytokines, growth factors, reactive oxygen species and their scavengers. MCs synthesize extracellular matrix related molecules, and the surface of MC microvilli secretes a highly hydrophilic protective barrier, “glycocalyx”, consisting mainly of glycosaminoglycans. MCs maintain a balance between procoagulant and fibrinolytic activation by producing a whole range of regulators, can synthetize fibrin and therefore form adhesions. Synthesis and recognition of hyaluronan and sialic acids might be a new insight to explain immunoactive and immunoregulatory properties of MCs. Epithelial to mesenchymal transition of MCs may involve serosal repair and remodeling. MCs might also play a role in the development and remodeling of visceral adipose tissue. Taken together, MCs play important roles in health and disease in serosal cavities of the body. The mesothelium is not just a membrane and should be considered as an organ.

Wilms' tumour 1 (WT1) in development, homeostasis and disease

“…Pre-eminent amongst these, as the name suggests, is the mesothelium that lines the body cavity and the organs therein. The mesothelium protects tissues from adhesion and plays key roles in fluid transport and inflammation (Kawanishi, 2016). However, over the past decade it has become clear that mesothelia are also a source of mesenchymal progenitors for diverse cell types within tissues, including fibroblasts and more specialised cells.…”

The peritoneal “soil” for a cancerous “seed”: a comprehensive review of the pathogenesis of intraperitoneal cancer metastases

“…The first line of defense is the peritoneal macrophages (PMs), which have the ability to generate significant amounts of the tumor necrosis factor (TNF). Their activity is followed by reactions elicited by PMCs which secrete a plethora of soluble mediators to the environment, such as cytokines (IL-1, IL-6, IL-15), chemokines (CXCL8/IL-8, CCL2/MCP-1, RANTES, CXCL1/GRO-1, and CXCL12/SDF-1), growth factors (TGF-β1, PDGF, FGF, and VEGF), ECM elements (collagens I, III, IV, fibronectin, elastin, and vitronectin), and adhesion molecules (ICAM-1, VCAM-1, E-cadherin) [ 62 ]. An important activity of the mesothelium is also the generation of the chemotactic gradient for polymorphonuclear leukocytes, which is related to the secretion of interleukin 17 [ 63 ].…”

“…They originate as fibroblasts from the mesoderm, but their appearance and function resemble that of epithelial cells; hence, PMCs express intermediate filaments typical of both the mesoderm (vimentin) and epithelium (cytokeratins). Under certain stimuli, in particular TGF-β1, PMCs lose their cobblestone appearance and adopt a spindle-shaped morphology typical of cells undergoing the EMT [ 62 ].…”

“…Among all the fractions of cells forming the peritoneal cavity, PMCs are the largest, and thus, their role in the maintenance of intraperitoneal homeostasis is the most prominent [ 62 ]. Their involvement in cancer metastases was also studied most extensively among all types of normal peritoneal cells, which is probably due to the fact that they have direct interaction with inflowing cancer cells as the first.…”

TMEM88 inhibits TGF-β1-induced-extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) program in human pleural mesothelial cells through modulating TGF-β1/Smad pathway

“…The pleura is lined by a monolayer of mesothelial cells that rest on a thin basement membrane [4]. Increasing evidence suggests that pleural mesothelial cells (PMCs) play a significant role in the pathogenesis of this condition through initiating inflammatory responses and producing ECM components [5,6]. Targeting PMCs may be adequate therapy and can be developed to prevent pleural fibrosis from occurring.…”