Proteins and mirnas in feline renal amyloid deposits

Amyloidosis is a group of diseases occurring in humans and animals, due to the deposition of misfolding proteins in different organs. In humans, deposits were characterized using proteomics and more recently the role of miRNAs in the pathogenesis was proposed. In Abyssinian cat the main target is the kidney. Little is known on the mechanisms underlying the disease. The aim of this study is to profile proteins and miRNAs in healthy and affected Abyssinian cats, to evaluate their differential expression and clarify the pathogenesis mechanisms. Formalin-fixed paraffin-embedded kidney slices were collected from 7 affected and 5 healthy Abyssinians and used for proteomic and miRNAs analyzes. Peptides were analyzed with an LTQ-Orbitrap Velos mass spectrometer (MS). MS spectra were searched against the F.catus NCBI sequence database (release31.01.2017) by MaxQuant. Bioinformatic analysis was performed with DAVID and Panther softwares. MiRNAs were sequenced on the Illumina NextSeq500 platform. MiRDeep2 was used to map reads on the genome vs9.0, identify putative miRNAs, quantify their expression and identify homologous. Filtered proteins and miRNs statistically different were identified using a student t-test and a moderate t-test respectively (p-value≤.05). Part of the proteins was exclusively detected in the affected (n.175), part in the healthy (n.47) and part were common to the two groups (n.160). A fraction of the latter resulted upregulated (n.16) or down regulated (n.18) in affected compared to the healthy cats (p-value≤.05). Annotation and functional grouping suggested an effect on extracellular matrix and macromolecular complex subunit organization. MiRNA analysis detected 341 representatives, 22 differentially expressed between affected and healthy (p<.05). Six miRNAs out of 22 (four with a P-value<.009) are known to be involved in Alzheimer Disease. Interestingly, miR-26a-5p (P-value 0.120) is involved in the human immunoglobulin light chain amyloidosis onset. This study identified different miRNA and protein renal compositions in Abyssinian affected and healthy cats. The pathways involving these molecules are under investigation, providing new insights for the pathogenesis understanding.