Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies

• DOI: 10.3389/fmed.2023.1122328
• Publication Date: 2023-03-13T05:34:55Z
• Authors: Chen-Fang Chung; Joan Papillon; José R. Navarro-B...; Julie Guillemette; Ameya Bhope; Amin Emad; Andrey V. Cybulsky
• Keywords: Glomerulosclerosis

Background Human glomerulonephritis (GN)—membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS) and IgA (IgAN), as well diabetic (DN) are leading causes of chronic kidney disease. In these glomerulopathies, distinct stimuli disrupt metabolic pathways in glomerular cells. Other pathways, including the endoplasmic reticulum (ER) unfolded protein response (UPR) autophagy, activated parallel to attenuate cell injury or promote repair. Methods We used publicly available datasets examine gene transcriptional glomeruli human GN DN identify drugs. Results demonstrate that there many common genes upregulated MN, FSGS, IgAN, DN. Furthermore, glomerulopathies were associated with increased expression ER/UPR autophagy genes, a significant number which shared. Several candidate drugs for treatment identified by relating signatures culture (“connectivity mapping”). Using assay correlates damage vivo , we showed one drug – neratinib (an epidermal growth factor receptor inhibitor) is cytoprotective. Conclusion The UPR multiple types injury. Connectivity mapping shared attenuated present study opens possibility modulating pharmacologically therapy GN.