Soluble betaglycan reduces renal damage progression in db/db mice
Soluble betaglycan reduces renal damage progression in db/db mice
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DOI：
10.1152/ajprenal.00264.2006
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Lopez-Casillas, Fernando
中科院分区：
文献类型：
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作者：
Juarez, Patricia;Vilchis-Landeros, M. Magdalena;Lopez-Casillas, Fernando
转化生长因子-β (TGF-β) 是肾脏疾病发病机制的关键介质。 Betaglycan，也称为 III 型 TGF-β 受体，通过调节 TGF-β 与 I 型和 II 型受体的接触来调节 TGF-β 的作用。 Betaglycan 增强 TGF-β；然而，由膜结合受体脱落产生的可溶性β聚糖是TGF-β的有效拮抗剂。在目前的工作中，我们使用重组形式的可溶性β聚糖（SBG）来预防遗传性肥胖和糖尿病db/db小鼠的肾损伤。八周龄的db/db或非糖尿病(db/m)小鼠腹膜内注射50μg SBG或单独的媒介物，每周3次，持续8周。接受媒介物的 db/db 小鼠出现白蛋白尿、血清肌酐升高以及肾小球系膜基质扩张。用 SBG 治疗的 db/db 小鼠表现出血清肌酐、白蛋白尿和结构性肾损伤的减少。这些作用与编码 TGF-β 1、TGF-β 2、TGF-β 3、IV 型胶原、I 型胶原、纤连蛋白和血清糖皮质激素激酶的 mRNA 肾脏水平降低以及 IV 型胶原和纤连蛋白免疫染色的减少有关。我们的数据表明，SBG 是一种肾脏保护剂，可以中和肾病模型中 TGF-β 的作用。由于 SBG 对所有 TGF-β 同工型（特别是 TGF-β 2）具有高亲和力，因此它天然存在于血清和组织中，并且其脱落可能受到调节。我们相信，SBG 将有助于长期治疗肾脏疾病和其他 TGF-β 发挥病理生理作用的疾病。
Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of renal diseases. Betaglycan, also known as the type III TGF-beta receptor, regulates TGF-beta action by modulating its access to the type I and II receptors. Betaglycan potentiates TGF-beta; however, soluble betaglycan, which is produced by the shedding of the membrane-bound receptor, is a potent antagonist of TGF-beta. In the present work, we have used a recombinant form of soluble betaglycan (SBG) to prevent renal damage in genetically obese and diabetic db/db mice. Eight-wk-old db/db or nondiabetic (db/m) mice were injected intraperitoneally with 50 mu g of SBG or vehicle alone three times a wk for 8 wk. The db/db mice that received vehicle presented albuminuria and increased serum creatinine, as well as glomerular mesangial matrix expansion. The db/db mice treated with SBG exhibited a reduction in serum creatinine, albuminuria, and structural renal damage. These effects were associated with lower kidney levels of mRNAs encoding TGF-beta 1, TGF-beta 2, TGF-beta 3, collagen IV, collagen I, fibronectin, and serum glucocorticoid kinase as well as a reduction in the immunostaining of collagen IV and fibronectin. Our data indicate that SBG is a renoprotective agent that neutralized TGF-beta actions in this model of nephropathy. Because SBG has a high affinity for all TGF-beta isoforms, in particular TGF-beta 2, it is found naturally in serum and tissues and its shedding may be regulated. We believe that SBG shall prove convenient for long-term treatment of kidney diseases and other pathologies in which TGF-beta plays a pathophysiological role.