Shuei-Liong Lin, Department and Graduate Institute of Physiology at NTUMC, Department of Internal Medicine at NTU Hospital
Chronic kidney disease poses a global health challenge, impacting approximately 15% of the population and placing significant strain on society and the economy. Despite the potential to slow down the progression of kidney disease by administering drugs that inhibit the renin-angiotensin-aldosterone system, kidney function continues to worsen in most patients possibly due to the diversity of disease etiologies and the lack of precise treatments. However, considerable progress has been made in understanding the underlying mechanism of many kidney diseases, such as the pathophysiology of diabetic kidney disease and ischemic kidney injury, and the role of APOL1 gene variants in patients of African ancestry with chronic kidney disease. In 2016, the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) initiated the Kidney Precision Medicine Project to develop personalized precision medicine by integrating clinical manifestations, kidney tissues, multiomics and imaging, and basic mechanistic studies (Figure 1). Our research in kidney precision medicine focuses on kidney pericytes, a cell type that maintains close contact with vascular endothelial cells through extensive branches. Kidney pericytes stabilize blood vessels and tissues by producing collagen and growth factors, as well as stabilize red blood cell count by producing erythropoietin. However, when the kidney is damaged, pericytes lose close contact with endothelial cells, proliferate and differentiate into numerous myofibroblasts, then lead to renal scarring, microvascular rarefaction, tubular atrophy, and loss of kidney function. Many genes are significantly methylated in pericytes of diseased kidneys (Figure 2). Nevertheless, we have shown that treatment with demethylating agents can promote the restoration of normal physiological function of kidney pericytes in diseased kidneys. Our ongoing project is developing a drug delivery system that can precisely target kidney pericytes to modify their epigenetic changes and restore their normal physiological function.
Figure 1: Clinical data, pathology, multiomics, digital atlas, and mechanistic studies of the kidneys integrated to develop precision medicine for kidney diseases.
Figure 2: Kidney injuries lead to pericyte transdifferentiation and the hypermethylation of genes such as
Epo and
Ybx2. Drugs targeting pericytes to modify their epigenetics have the potential to restore normal physiological function.
