Excellence Centre for Research, Transfer and High Education for the development of De Novo Therapies (DENOTHE), University of Florence, Florence, Italy.
J Am Soc Nephrol. 2010 Oct;21(10):1612-9. doi: 10.1681/ASN.2010010048. Epub 2010 Sep 9.
Global glomerulosclerosis with loss of podocytes in humans is typical of end-stage renal pathology. Although mature podocytes are highly differentiated and nondividing, converging evidence from experimental and clinical data suggests adult stem cells within Bowman's capsule can rescue some of this loss. Glomerular epithelial stem cells generate podocytes during kidney growth and regenerate podocytes after injury, thus explaining why various glomerular disorders undergo remission occasionally. This regenerative process, however, is often inadequate because of inefficient proliferative responses by glomerular epithelial stem cells with aging or in the setting of focal segmental glomerulosclerosis. Alternatively, an excessive proliferative response by glomerular epithelial stem cells after podocyte injury can generate new lesions such as extracapillary crescentic glomerulonephritis, collapsing glomerulopathy and tip lesions. Better understanding of the mechanisms that regulate growth and differentiation of glomerular epithelial stem cells may provide new clues for prevention and treatment of glomerulosclerosis.
人类的全球肾小球硬化症伴有足细胞丧失，是终末期肾脏病理的典型特征。尽管成熟的足细胞高度分化且不分裂，但来自实验和临床数据的综合证据表明，鲍曼囊中的成体干细胞可以挽救部分足细胞的丧失。肾小球上皮干细胞在肾脏生长过程中产生足细胞，并在损伤后再生足细胞，这就解释了为什么各种肾小球疾病偶尔会自行缓解。然而，由于肾小球上皮干细胞随年龄增长或在局灶性节段性肾小球硬化症中的增殖反应效率低下，这种再生过程往往是不充分的。或者，足细胞损伤后肾小球上皮干细胞的过度增殖反应会产生新的病变，如细胞外新月体性肾小球肾炎、塌陷性肾小球病和顶端病变。更好地了解调节肾小球上皮干细胞生长和分化的机制可能为预防和治疗肾小球硬化症提供新的线索。
