首页|Decorating Histones in Polycystic Kidney Disease
Decorating Histones in Polycystic Kidney Disease
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
Amer Soc Nephrology
Autosomal dominant polycystic kidney disease (ADPKD) is perhaps the most common monogenetic condition known to humankind. The pathologic hallmark is the presence of innumerable fluid-filled tissue sacs called cysts that inundate the renal parenchyma. The cysts are derived from renal tubules, primarily the collecting duct, and are lined by a single layer of epithelial cells that exhibit high proliferation and excessive fluid secretion. Over years and decades, the relentless growth in cyst volume eventually produces massive bilateral kidneys and results in kidney failure in nearly 50% of individuals with ADPKD. The inciting molecular event in virtually all clinically relevant cases is a monoallelic loss-of-function mutation of the PKD1 gene or the PKD2 gene. The precise sequence of events that unfold next is not entirely clear, but we know that multiple signaling cascades get activated. The cAMP pathway is the best studied, and its deregulation is the basis for using tolvaptan, the only Food and Drug Administration-approved treatment for ADPKD. However, the list of deregulated pathways is long and ever expanding. It includes many notable oncogenic and proprolifer-ative pathways, such as c-Myc, STAT, mammalian target of rapamycin, YAP/TAZ, microRNAs, and many other signaling pathways. Not surprisingly, this widespread dysregulation is facilitated by and leads to genome-wide transcriptomic rewiring. How does polycystic kidney disease (PKD) gene loss unleash this broad aberrant signaling? Is there a method behind this madness? There cannot be a single simple answer, but emerging evidence suggests that one clue may be to look at the epigenome.
Harini Ramalingam、Vishal Patel
展开 >
Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical
NSTL
Amer Soc Nephrology
