TLR-4 Signaling in Pericytes

Introduction Pericytes are cells with intriguing properties that have only recently attracted the attention of numerous researchers. In the past years, their function was mainly associated with microvascular homeostasis, angiogenesis and maintenance of bloodtissue barriers. Recently, several studies suggest that pericytes play a predominant role in acute as well as chronic diseases contributing to damage or tissue repair in an organ specific manner. Given their role in inflammatory and fibrotic context, the activation of pericyte Toll like Receptor-4 (TLR-4) signaling was suggested as a powerful molecular mechanism of pericytes activation and dysfunction. Here we review emerging works regarding the involvement of the TLR-4 signaling in pericytes activation both in healthy and pathological conditions. Methods For the selection of literature cited we used MEDLINE/Pubmed database and in particular the MESH vocabulary. The keywords used in the MEDLINE research were: pericytes; TLR-4 signaling; MyD88 pathway, mesenchymal stem cells; pericyte to myofibroblast transition (PMT); endotoxin; LPS and LPS-Binding protein (LBP). Results Brain and lung pericytes are sensitive to microbial or non-microbial injury by TLR-4 signaling and exhibit non-professional Antigen-Presenting Cell (APC) characteristics suggesting a prominent role in immunosurveillance. Moreover, renal pericytes activate fibrogenesis via the TLR-4 and MyD88-dependent mechanism. TLR-4 signaling has been reported to be pivotal in various pathological conditions, including cardiovascular diseases, neuronal degeneration and correlated disorders, sepsis, lung and renal diseases. Conclusions There is an urgent need for exploring TLR-4 signaling in different pericyte populations in order to develop new therapeutic approaches trying to modulate their behavior in pathological conditions.