Role of growth and transcription factors in tubulointerstitial injury in diabetes

进行性肾脏疾病的发生是一系列分子和细胞途径的结果。肾脏疾病最常见的原因之一是糖尿病，这似乎部分与某些生长因子（如CTGF）的表达和作用增加有关。这些因素促进了肾脏瘢痕组织的沉积，其中一种促进瘢痕形成的方式是改变细胞的行为，使其生成胶原蛋白。该提案不仅将关注CTGF如何促进瘢痕形成，还将探索两种名为Snail和Slug的新因子，它们可以直接作用于CTGF等特定基因以抑制这些有害影响。通过进一步表征肾脏中涉及蜗牛、蛞蝓和CTGF的这些途径，将有可能为包括糖尿病肾病在内的各种形式的进行性肾脏疾病产生新的靶点和治疗方法。

Progressive kidney disease occurs as a result of a range of molecular and cellular pathways. One of the commonest causes of kidney disease is diabetes and this appears to be partly related to increased expression and action of certain growth factors such as CTGF. These factors promote the deposition of scar tissue in the kidney and one of the ways these promote this scarring is to change a cell s behaviour so that it now lays down collagen. This proposal will not only focus on how CTGF promotes scarring but will explore 2 novel factors called Snail and Slug which can act directly on particular genes such as CTGF to inhibit these deleterious effects. By further characterising these pathways involving Snail, Slug and CTGF in the kidney it will be possible to generate new targets and therapies for various forms of progressive kidney disease including diabetic kidney disease.