Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.
Mangesh KulkarniAleksandra LeszczynskaGabbie WeiMichael A WinklerJie TangVincent A FunariNan DengZhenqiu LiuVasu PunjSophie X DengAlexander V LjubimovMehrnoosh SaghizadehPublished in: Scientific reports (2017)
Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.
Keyphrases
- endothelial cells
- wound healing
- type diabetes
- glycemic control
- stem cells
- gene expression
- induced pluripotent stem cells
- signaling pathway
- pluripotent stem cells
- end stage renal disease
- cell proliferation
- optical coherence tomography
- cardiovascular disease
- chronic kidney disease
- squamous cell carcinoma
- dna methylation
- newly diagnosed
- peritoneal dialysis
- genome wide
- bone marrow
- adipose tissue
- prognostic factors
- weight loss
- rectal cancer
- cataract surgery
- patient reported