111年8月11日(四)12:30於3樓和氣會議室舉辦「研究發想會」,由國防醫學院教育長兼微生物及免疫學科暨研究所吳家兆教授主講「褪黑激素、晝夜週期與膜性腎病變」,歡迎有興趣的同仁前往聆聽。
本次講座摘要:
Membranous nephropathy (MN), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Initially, our results suggest that melatonin treatment ameliorates experimental MN via multiple pathways, including by its antioxidative, antiapoptotic, and immunomodulatory effects. Although it is known that melatonin plays a protective role in MN, the role of melatonin receptors in the pathophysiology of MN is unclear. Following, we found that melatonin receptor 1A (MTNR1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that in MN kidney tissue, decreased PITX1 expression at the MTNR1A promoter regions leads to decreased levels of MTNR1A in renal tubular epithelial cells, which increases the future risk of MN. However, knowledge of the mechanism underlying MTNR1A expression has been limited and identified cytoplasmic hnRNPL as a novel player in the upregulation of MTNR1A expression in renal tubular epithelial cells, and as a potential therapeutic target. We further provide the molecular basis of c-Fos in transcriptionally downregulating expression of AANAT and melatonin, and elucidate the protective role of AANAT in preventing renal tubular cells death in albumin-injury cell model and MN progression. Melatonin, circadian and MN are linked together. We know smoking and sleeping disorder have been associated with chronic kidney disease (CKD). We showed that sleeping pill use was related to an increased risk of CKD and ESRD. There are interactions of smoking and sleep on the renal function. The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers. Sleep disorder is bi-directionally associated with chronic kidney diseases (CKD). We also analyze the interaction between sleep duration on weekdays/weekends, catch-up sleep on weekends, and kidney functions to elucidate the missing link.