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Single cell analysis reveals the heterogeneity of fibroblasts in the diabetic heart

ABSTRACT: Diabetes mellitus is one of the most chronic diseases, of which diabetic cardiomyopathy is the major cause of morbidity and involves in multiple processes such as inflammation, oxidative stress, fibrosis, extracellular collagen deposition, apoptosis, mitochondria dysfunction. However, the exact mechanisms of fibroblasts concerning type Ⅰ diabetes remain unclear. To further understand the functional roles of fibroblasts of STZ-induced diabetic mice, we lead the single cell RNA sequence. Cells were comprised of endothelial, fibroblast, cardiomyocyte, smooth muscle cells, macrophage and other type cells. Single cell sequence illustrates novel fibroblast sub-clusters and highlight the role of Lox. Real-time quantitative PCR, western blotting, immunofluorescence was used to verify the sequence data. We validate the dysfunctions of diabetic cardiomyopathy by echocardiogram. Our study supports novel insights into the pathogenesis of diabetic cardiomyopathy.

ORGANISM(S): Mus musculus

PROVIDER: GSE213337 | GEO | 2023/01/31

REPOSITORIES: GEO

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Project description:Patients with long-duration diabetes develop cardiovascular complications resulting in highly increased mortality and complications which affect the kidneys, eyes and peripheral nerves associated with high morbidity. Among the diabetic complications, damage in the eye, diabetic retinopathy, is the most common microvascular complication of diabetes. Diabetic retinopathy is a leading cause of vision-loss globally. It is characterized by a number of different patho-mechanisms including changes in vascular permeability, capillary degeneration, and finally at a late stage overshooting formation of new blood vessels. This expression analysis focused on the use of different experimental models for Diabetes Mellitus and its complications (for a review see 1: Al-Awar et al: Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; doi: 10.1155/2016/9051426). By that, we wanted to uncover the relative contributions of systemic hyperinsulinaemia and/or hyperglycemia to molecular regulations. The following models have been used: As insulinopenic, hyperglycemic model reflecting Type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p.) were used. Wistar rats without STZ injection served as non-diabetic controls. Male obese ZDF rats (Fa/Fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male lean ZDF rats (Fa/-) served as non-diabetic controls. Male obese ZF rats (Fa/Fa) hyperglycemia were used reflecting euglycemia and severe insulin resistance. Male lean ZF rats (Fa/-) served as controls. ZDF and ZF rats were obtained in two genotypes, obese (genotype fa/fa) and lean littermates (genotype Fa/?). All rats were housed in standard cages under a normal light-dark cycle for 16 weeks. All animals had free access to food and water. ZF and Wistar rats received a standard chow (Ssniff R/M) and ZDF rats received Purina 5008 chow. A group size of n=8 were used for all study groups. Wistar rats were rendered type-1 like hyperglycemic and hypoinsulinemic via a single injection of streptocotocin (STZ, 60mg/kg; i.p.) at 7 weeks of age. Obese ZDF rats (fa/fa) develop spontaneously a type-2 diabetes phenotype with persisting hyperglycemia and transient hyperinsulinemia (hyperglycemic, hypoinsulinemic). Obese ZF rats (fa/fa) develop insulin resistance with permanent hyperinsulinemia without concomitant hyperglycemia and no overt diabetes phenotype. Non STZ treated Wistar rats, lean ZDF littermates (Fa/?), and lean ZF littermates (Fa/?) served as controls. All groups were kept for 12 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays.

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Single cell analysis reveals the heterogeneity of fibroblasts in the diabetic heart

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