Invoking the power of thrombospondins: regulation of thrombospondins expression

Abstract

Increasing evidence suggests critical functions of thrombospondins (TSPs) in a variety of physiological and pathological processes. With the growing understanding of the importance of these matricellular proteins, the need to understand the mechanisms of regulation of their expression and potential approaches to modulate their levels is also increasing. The regulation of TSP expression is multi-leveled, cell- and tissue-specific, and very precise. However, the knowledge of mechanisms modulating the levels of TSPs is fragmented and incomplete. This review discusses the known mechanisms of regulation of TSP levels and the gaps in our knowledge that prevent us from developing strategies to modulate the expression of these physiologically important proteins.

Keywords: Regulation of expression; Thrombospondin; Transcription; Translation; miRNA.

Figure 1. Common DNA sequence motifs in the promoters of TSPs

The analysis of the promoters of TSP-1, TSP-2, TSP-3, TSP-4 and COMP was performed using SCOPE motif finder (http://genie.dartmouth.edu/scope) (31, 32). Motifs positioned similarly in the promoters of two or more TSPs are shown in the figure (6 out of 20 most significant matches).

Figure 2. Expression of TSPs in human tissues and organs, comparison to tenascin C, SPARC and fibronectin expression

The figure was prepared using the data from the database http://expression.gnf.org (33). Organs from left to right: cerebellum, whole brain, cortex, caudate nucleus, amygdala, thalamus, corpus collosum, spinal cord, whole blood, testis, pancreas, placenta, pituitary gland, thyroid, prostate, ovary, uterus, DRG, salivary gland, trachea, lung, thymus, spleen, adrenal gland, kidney, liver, heart.

Figure 3

Promoter of TSP-1: regulatory regions and experimentally confirmed binding sites for transcription factors.