Protecting Podocytes: A Key Target for Therapy of Focal Segmental Glomerulosclerosis.
Protecting Podocytes: A Key Target for Therapy of Focal Segmental Glomerulosclerosis.
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DOI：
10.1159/000481634
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发表时间：
2018
影响因子：
4.2
通讯作者：
Tumlin JA
中科院分区：
文献类型：
--
作者：
Campbell KN;Tumlin JA
局灶节段性肾小球硬化症 (FSGS) 是肾活检证实的一种损伤组织学模式，可能由多种原因和机制引起。据估计，其发病率为百万分之七，是美国最常见的导致终末期肾病的原发性肾小球疾病。本综述重点关注 FSGS 患者足细胞的损伤以及这种损伤的后果、FSGS 的遗传学以及治疗方法，重点关注对足细胞的影响。足细胞是肾小球滤过屏障的核心，由于其高度分化的有丝分裂后表型而特别脆弱。 FSGS病理学中涉及的进行性结构变化包括足细胞足突消失、足细胞死亡和肾小球基底膜暴露、非特异性血浆蛋白过滤、毛细血管扩张、粘连点的错误过滤和系膜基质增殖。虽然足细胞的损伤和死亡可能是由单基因疾病引起的，但有证据还表明可溶性因子（例如可溶性尿激酶型纤溶酶原激活剂受体、心肌营养素样细胞因子-1和抗 CD40 抗体）在促进 FSGS 移植后复发的作用。几类药物，包括皮质类固醇、钙调神经磷酸酶抑制剂、内皮素受体拮抗剂、促肾上腺皮质激素和利妥昔单抗，已被证明可有效治疗 FSGS，并对足细胞具有显着的保护作用。更好地了解足细胞生物学对于确定治疗 FSGS 患者的新治疗靶点和药物至关重要。
Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury demonstrated by renal biopsy that can arise from a diverse range of causes and mechanisms. It has an estimated incidence of 7 per 1 million and is the most common primary glomerular disorder leading to end-stage renal disease in the United States. This review focuses on damage to the podocyte and the consequences of this injury in patients with FSGS, the genetics of FSGS, and approaches to treatment with a focus on the effects on podocytes. The podocyte is central to the glomerular filtration barrier and is particularly vulnerable because of its highly differentiated post-mitotic phenotype. The progressive structural changes involved in the pathology of FSGS include podocyte foot process effacement, death of podocytes and exposure of the glomerular basement membrane, filtration of nonspecific plasma proteins, expansion of capillaries, misdirected filtration at points of synechiae, and mesangial matrix proliferation. Although damage to and death of podocytes can result from singlegene disorders, evidence also suggests a role for soluble factors, such as soluble urokinase-type plasminogen activator receptor, cardiotrophin-like cytokine-1, and anti-CD40 anti-bodies, that promote FSGS recurrence post transplant. Several classes of medications, including corticosteroids, calcineurin inhibitors, endothelin receptor antagonists, adrenocorticotropic hormone, and rituximab, have been shown to be effective for the treatment of FSGS and have been demonstrated to have significant protective effects on podocytes. Greater understanding of podocyte biology is essential to the identification of new treatment targets and medications for the management of patients with FSGS.
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影响因子：
4.6
作者：
Alfano M;Cinque P;Giusti G;Proietti S;Nebuloni M;Danese S;D'Alessio S;Genua M;Portale F;Lo Porto M;Singhal PC;Rastaldi MP;Saleem MA;Mavilio D;Mikulak J
通讯作者：
Mikulak J
影响因子：
15.9
作者：
Daehn, Ilse;Casalena, Gabriella;Bottinger, Erwin P.
通讯作者：
Bottinger, Erwin P.
影响因子：
6.2
作者：
Garrouste, Cyril;Canaud, Guillaume;Heng, Anne Elisabeth
通讯作者：
Heng, Anne Elisabeth
影响因子：
82.9
作者：
Beckerman P;Bi-Karchin J;Park AS;Qiu C;Dummer PD;Soomro I;Boustany-Kari CM;Pullen SS;Miner JH;Hu CA;Rohacs T;Inoue K;Ishibe S;Saleem MA;Palmer MB;Cuervo AM;Kopp JB;Susztak K
通讯作者：
Susztak K
DOI：
10.1152/ajprenal.00231.2015
发表时间：
2016-05-01
影响因子：
4.2
作者：
Elvin, Johannes;Buvall, Lisa;Haraldsson, Borje
通讯作者：
Haraldsson, Borje