Eom Minseob, Hudkins Kelly L, Alpers Charles E
aDepartment of Pathology, University of Washington School of Medicine, Seattle, Washington, USA bDepartment of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Curr Opin Nephrol Hypertens. 2015 May;24(3):245-51. doi: 10.1097/MNH.0000000000000112.
Foam cells in human glomeruli can be encountered in various renal diseases including focal segmental glomerulosclerosis and diabetic nephropathy. Although foam cells are key participants in atherosclerosis, surprisingly little is known about their pathogenicity in the kidney. We review our understanding (or lack thereof) of foam cells in the kidney, as well as insights gained in studies of foam cells and macrophages involved in atherosclerosis to suggest areas of investigation that will allow better characterization of the role of these cells in renal disease.
There is a general dearth of animal models of disease with renal foam cell accumulation, limiting progress in our understanding of the pathobiology of these cells. Recent genetic modifications of hyperlipidemic mice have resulted in some new disease models with renal foam cell accumulation. Recent studies have challenged older paradigms by findings that indicate that many tissue macrophages are derived from cells permanently residing in the tissue from birth rather than circulating monocytes.
Renal foam cells remain an enigma. Extrapolating from studies of atherosclerosis suggests that therapeutics targeting mitochondrial reactive oxygen species production, or modulating cholesterol and lipoprotein uptake or egress from these cells, may prove beneficial for kidney diseases in which foam cells are present.
人类肾小球中的泡沫细胞可见于多种肾脏疾病,包括局灶节段性肾小球硬化症和糖尿病肾病。尽管泡沫细胞是动脉粥样硬化的关键参与者,但令人惊讶的是,我们对它们在肾脏中的致病性知之甚少。我们回顾了我们对肾脏中泡沫细胞的理解(或缺乏理解的情况),以及在动脉粥样硬化中对泡沫细胞和巨噬细胞研究中获得的见解,以提出一些研究领域,这些领域将有助于更好地描述这些细胞在肾脏疾病中的作用。
普遍缺乏肾脏中有泡沫细胞积聚的疾病动物模型,这限制了我们对这些细胞病理生物学的理解进展。最近对高脂血症小鼠的基因改造产生了一些新的有肾脏泡沫细胞积聚的疾病模型。最近的研究通过一些发现对旧范式提出了挑战,这些发现表明许多组织巨噬细胞源自出生时就永久存在于组织中的细胞,而非循环单核细胞。
肾脏泡沫细胞仍然是一个谜。从动脉粥样硬化研究推断,针对线粒体活性氧产生、或调节这些细胞中胆固醇和脂蛋白摄取或流出的治疗方法,可能对存在泡沫细胞的肾脏疾病有益。