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Review
. 2018 Jul;75(13):2339-2354.
doi: 10.1007/s00018-018-2805-0. Epub 2018 Mar 29.

Follistatin-like 1 in development and human diseases

Andrea Mattiotti  1 , Stuti Prakash  1 , Phil Barnett  1 , Maurice J B van den Hoff  2
Affiliations
Review

Follistatin-like 1 in development and human diseases

Andrea Mattiotti et al. Cell Mol Life Sci. 2018 Jul.

Abstract

Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively studied over the last years, though its mechanism of action remains elusive. FSTL1 is involved in multiple signaling pathways and biological processes, including vascularization and regulation of the immune response, a feature that complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been shown, but other molecular partners probably exist. During cancer progression and rheumatoid arthritis, controversial data have been reported with respect to the proliferative, apoptotic, migratory, and inflammatory effects of FSTL1. This controversy might reside in the extensive post-transcriptional regulation of FSTL1. The FSTL1 primary transcript also encodes for a microRNA (miR-198) in primates and multiple microRNA-binding sites are present in the 3'UTR. The switch between expression of the FSTL1 protein and miR-198 is an important regulator of tumour metastasis and wound healing. The glycosylation state of FSTL1 is a determinant of biological activity, in cardiomyocytes the glycosylated form promoting proliferation and the non-glycosylated working anti-apoptotic. Moreover, the glycosylation state shows differences between species and tissues which might underlie the differences observed in in vitro studies. Finally, regulation at the level of protein secretion has been described.

Keywords: Cancer; Cardiovascular disease; Fibrosis; Glycosylation; Immune disease; Inflammation; Obesity; Pulmonary disease; Signal transduction; miRNA.

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Figures

Fig. 1
Fig. 1
Follistatin-like 1 in cardiovascular disease. Schematic representation of the known signaling pathways interacting with FSTL1 in cardiovascular disease. Grey components indicate unknown receptors. The coloured arrows denote the secreted Fstl1 (width relates amount). Coloured area defines different conditions. Image adjusted from http://smart.servier.com
Fig. 2
Fig. 2
Follistatin-like 1 in cancer and tumour. Schematic representation of the known signaling pathways interacting with FSTL1 during cancer growth and metastasis. Grey components indicate unknown receptors. Helical structures represent gene expression. Dashed arrow indicates translation from mRNA to protein. The dashed line separates different processes: tumour growth and metastasis. Image adjusted from http://smart.servier.com
Fig. 3
Fig. 3
Follistatin-like 1 in immune diseases. Schematic representation of the known signaling pathways interacting with FSTL1 during inflammatory processes. Grey components indicate unknown receptors. Helical structures represent gene expression. Dashed arrow indicates translation from mRNA to protein. The dashed line separates the two opposite effects of FSTL1: pro- and anti-inflammatory. Image adjusted from http://smart.servier.com
See this image and copyright information in PMC

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