Transcriptomic profiling of polycystic kidney disease identifies paracrine factors in the early cyst microenvironment

Biochim Biophys Acta Mol Basis Dis. 2023 Dec 7:166987. doi: 10.1016/j.bbadis.2023.166987. Online ahead of print.ABSTRACTInitial cysts that are formed upon Pkd1 loss in mice impose persistent stress on surrounding tissue and trigger a cystic snowball effect, in which local aberrant PKD-related signaling increases the likelihood of new cyst formation, ultimately leading to accelerated disease progression. Although many pathways have been associated with PKD progression, the knowledge of early changes near initial cysts is limited. To perform an unbiased analysis of transcriptomic alterations in the cyst microenvironment, microdomains were collected from kidney sections of iKsp-Pkd1del mice with scattered Pkd1-deletion using Laser Capture Microdissection. These microdomains were defined as F4/80-low cystic, representing early alterations in the cyst microenvironment, F4/80-high cystic, with more advanced alterations, or non-cystic. RNA sequencing and differential gene expression analysis revealed 953 and 8088 dysregulated genes in the F4/80-low and F4/80-high cyst microenvironment, respectively, when compared to non-cystic microdomains. In the early cyst microenvironment, several injury-repair, growth, and tissue remodeling-related pathways were activated, accompanied by mild metabolic changes. In the more advanced F4/80-high microdomains, these pathways were potentiated and the metabolism was highly dysregulated. Upstream regulator analysis revealed a series of paracrine factor...

Source: Biochimica et Biophysica Acta - December 9, 2023 Category: Biochemistry Authors: Sevtap A Yasinoglu Thomas B Kuipers Ernst Suidgeest Louise van der Weerd Hailiang Mei Hans J Baelde Dorien J M Peters Source Type: research