TP B1: Expression and function of the non-coding WISP1 transcript (IncWISP1) in fibrosis

Chronic interstitial deregulation of tissue homeostasis (parainflammation) is a risk factor for fibrosis and carcinogenesis. The mechanisms of unbalanced tissue homeostasis involve altered transcriptional and post-transcriptional regulatory mechanisms, including non-coding RNAs such as microRNAs (miR) or long non-coding RNAs (lncRNAs). LncRNAs belong to a rapidly growing class of RNAs and are defined as non-coding transcripts longer than 200 nucleotides. They are involved in processes like chromatin modification, transcriptional and post-transcriptional gene regulation. For example, lncRNAs have been shown to sequester miRNAs and thereby promote the expression of miRNA-target genes (sponge-like action).

Wnt1-inducible signaling pathway protein 1 (WISP1) is involved in organ development but also in fibrogenic and cancerous tissue alterations. It belongs to the CCN family of connective tissue growth factors and is canonically regulated by the Wnt1/β-catenin pathway. Also, some splice variants and other alternative transcripts expressed from the WISP1 locus with mostly unknown function have been described. Some of these appear to act as non-coding RNAs. Our recent data showed that an alternative WISP1 transcript is upregulated by different cell stressors in renal cells leading to the increased formation of extracellular matrix (ECM) components such as collagens. This suggests a role of the WISP1 locus in pathological cellular processes, in particular fibrosis. Accordingly, the identification and characterization of triggers and mechanisms involved in WISP1 RNA-induced deregulation of tissue homeostasis may contribute to the understanding of organ and tissue remodeling and malfunction. These studies have to address: 1) relevant cell stressors; 2) signaling pathways involved in non-coding RNA expression; 3) interactions of non-coding RNAs and their crosstalk with target gene expression.