Olink Target 96 Mouse Exploratory Panel

Diabetic kidney disease (DKD) stands as the leading cause of renal failure. The advancement of therapeutic agents has been hindered by our incomplete understanding of animal models at the cellular level. Researchers have identified that ZSF1 rats replicate human DKD both phenotypically and at the transcriptomic level. Through tensor decomposition, the proximal tubule (PT) and interstitial matrix were highlighted as phenotype-associated cell types, displaying a continuous lineage relationship. Given that DKD involves endothelial dysfunction, oxidative stress, and nitric oxide depletion, soluble guanylate cyclase (sGC) emerges as a promising drug target for DKD. sGC expression is specifically enriched in the PT and interstitial matrix. In ZSF1 rats, pharmacological activation of sGC provided significant benefits compared to stimulation, mechanistically linked to improved oxidative stress regulation, thereby enhancing downstream cGMP effects. Furthermore, the authors identified an sGC gene co-expression module that enables stratification of human kidney samples based on DKD prevalence and disease-related metrics such as renal function, proteinuria, and fibrosis, underscoring the relevance of the sGC pathway in patients.

The majority of the data were derived from bulk and single-cell RNA sequencing (RNAseq), immunohistochemistry, and other techniques. The Olink mouse panel was utilized to measure 92 plasma proteins associated with DKD (specific detection data can be found in the supplementary materials of the original article, with partial protein results shown in the figure below). The results highlighted in the article indicate that in diabetic ZSF1 rats, the levels of eight proteins (100%) detected by the Olink mouse panel were significantly elevated, further underscoring the similarity between the ZSF1 rat model and human DKD. These proteins are involved in a variety of biological functions, including development (DLL1, MATN2), inflammation (EDA2R, IL17F, CCL5, TNFSF12), and transforming growth factor-beta (TGFβ) signaling (FSTL3, TGFBR3).

Figure 1. Explorative proteomics analysis of 92 plasma proteins. (Balzer, M. S., et al. 2024)