A gene¹ called PVT1 may help reduce the kidneys ability to filter blood, leading to kidney disease, kidney failure and death, according to a study published today by researchers at the Translational Genomics Research Institute (TGen). The TGen team found PVT1 expression levels increased up to 5-fold in response to hyperglycemia（高血糖症） , or high blood sugar, a condition that often accompanies diabetes².

But by knocking down or reducing the expression of the PVT1gene, TGen researchers lowered the amount of proteins associated with the excessive accumulation of extracellular matrix (ECM细胞外基质) in glomeruli（肾小球） , part of the basic filtration unit of kidneys, according to the TGen study published today in the online scientific journal Public Library of Science (PLoS) ONE.

The accumulation of excessive ECM within the mesangial cells, which regulate blood flow in capillaries⁴ inside the kidney, is a hallmark of diabetic nephropathy（肾病） , or kidney disease, which is the leading cause of reduced life expectancy⁵ among the nation's growing numbers of diabetics.

"The goal of this study was to identify possible molecular⁶ mechanisms⁷ by which PVT1 may contribute to the development and progression of diabetic nephropathy in mesangial cells," said Dr. Johanna DiStefano, the study's senior author and Director of TGen's Diabetes, Cardiovascular and Metabolic⁸ Diseases Center.

"Despite the growing magnitude of the disease, the molecular mechanisms underlying⁹ the etiology（病因学） of diabetic nephropathy remain poorly understood," Dr. DiStefano said.

PVT1, also known as plasmacytoma（浆细胞瘤） variant¹⁰ translocation 1, was previously¹¹ identified by Dr. DiStefano's team as a candidate gene for End Stage Renal Disease (ESRD), or kidney failure. Too much PVT1 also has been associated with breast and ovarian cancers, in which it may help cause cells to multiply out of control and fail to go through the normal process of cellular³ death.

Through RNA interference, which helps control which genes¹² are active and the degree of their activity, researchers reduced the expression of PVT1, which in turn reduced the protein levels of ECM components¹⁴.

In a related finding, TGen scientists discovered that PVT1 affects the expression of other genes — FN1, COL4A1 and PAI-1 — in a manner that is at least partially¹⁵ independent of TFFB1, a gene associated with tissue fibrosis（纤维化） , or tissue damage.

"Delineation¹⁶（描述） of the relationship between TGFB1 and PVT1 represents a critical component¹³ toward understanding the molecular mechanisms underlying the regulation of ECM in diabetic nephropathy," said Dr. Lucrecia Alvarez, the study's lead author and a TGen post-doctoral fellow.