Identification of Lumican as a New Common Biomolecule for Heart Failure and Diabetic Kidney Disease by Integrated Bioinformatics Analysis

Background: Both of heart failure (HF) and diabetic kidney disease (DKD) are common complications of type 2 diabetes mellitus, which have close pathophysiological interactions to form vicious cycle and aggravate the development of both diseases. Renin-angiotensin-aldosterone system and sodium-dependent glucose transporters 2 are major common therapeutic targets for HF and DKD, while there are few studies focusing on the common inflammatory process in myocardium in HF and tubulointerstitium in DKD. In this study, we aimed to identify the common inflammatory process and biomolecules in the pathogenesis of HF and DKD, and wished to bring new common therapeutic targets for HF and DKD. Methods: Gene expression profiling data from myocardium in HF patients, tubulointerstitium in DKD patients, and the corresponding healthy controls were acquired from the GEO database. R packages were used for the data processing. We defined the common differentially expressing genes mostly correlated with the onset of HF and DKD as the key genes in this study. HF mice established by left coronary artery ligation and db/db mice, and the myocardial cell line (AC-16) and the proximal tubular epithelial cell (PTEC) line (HK-2) were used to validate the bioinformatic findings in this study. Results: LUM (lumican) was identified as the key gene after differential expression analysis and weighted correlation network analysis. Gene set enrichment analysis revealed that the function of LUM was positively enriched in antigen processing and presentation, collagen fibril organization, Wnt signaling pathway and response to transforming growth factor β, suggesting that lumican might be regulated by Wnt signaling pathway and could enhance extracellular matrix organization to promote fibrosis in both HF and DKD. Lumican upregulation was mainly located in the inner layer of myocardium in HF mice and in PTECs in db/db mice. In HK-2 and AC-16 cell line, lumican was only upregulated in the combined stimulation of hypoxia and high glucose while its expression level remained constant in separate hypoxia or high glucose induction. Conclusion: We identified lumican as a new common biomolecule involved in the pathogenesis of HF and DKD. Lumican might be upregulated by Wnt signaling pathway in both HF and DKD.