The role of discoidin domain receptor tyrosine kinase 1 in the process of fibrosis
Gene transcription regulation is an important process in the context of disease progression. Our lab is interested in fibrosis, so we will focus our attention on collagen type I and type IV production. Receptor Tyrosine Kinases (RTKs) have been largely shown to be important in various cellular processes and nuclear RTKs have been shown to be important for gene transcription regulation. Out of all the RTKs, we focus our attention toward discoidin domain receptor tyrosine kinase 1 (DDR1). DDR1 has been shown to be important in cell migration, adhesion, tissue homeostasis, as well as in fibroproliferative diseases. Our hypothesis is that DDR1 can translocate into the nucleus of the cells and promote extracellular matrix production. In order to study DDR1 as a nuclear RTK, we transfected HEK293 cells with DDR1-GFP and GFP followed by collagen type I treatment for different time points and checked the nuclear level of DDR1 by nuclear fractionation followed by Western Blot analysis and microscopy. In order to study DDR1 in the context of gene regulation, we checked the levels of collagen type I and IV in DDR1 overexpressing HEK293. Our preliminary data shows nuclear accumulation of DDR1 and increased collagen type IV production after collagen type I treatment. We can speculate a possible role of DDR1 in gene transcription regulation and its role in disease progression. To this end we believe that inhibition of DDR1 can be beneficial in the regression of fibroproliferative diseases.