Stanniocalcin supports the functional adaptation of adult-sized kidneys transplanted into the pediatric recipients.
Stanniocalcin supports the functional adaptation of adult-sized kidneys transplanted into the pediatric recipients.
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斯钙素支持移植到儿科受者体内的成人肾脏的功能适应。
DOI：
10.1097/tp.0b013e31824f3d56
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发表时间：
2012
期刊：
影响因子：
6.2
通讯作者：
Sarwal,Minnie
中科院分区：
文献类型：
--
作者：
Lee,Sangho;Naesens,Maarten;Li,Li;Sarwal,Minnie
背景成人肾（ASK）移植物对受者尺寸的功能适应并不完全可逆，并且与最小受者的不可逆组织学损伤有关。本研究的目的是揭示 ASK 移植对小型儿科受者功能适应的分子机制。方法由于婴儿 ASK 的生理和功能适应在移植后 3 个月时观察到最多，因此我们选择了 21 名 ASK 儿科受者，在植入时以及 3 个月和 6 个月时进行了方案活检，没有延迟移植功能或间隔排斥，并且我们在 3 个月和 3 个月时对同种异体肾移植物活检进行了全基因组表达谱分析。将结果与随后的绝对肾小球滤过率 (aGFR) 相关联。结果 724 个独特基因与 aGFR 显着相关（q 值 < 5%）。规范途径分析发现参与调节肾小管盐重吸收和器官发育和肥大的酶途径的相关途径过多。与 aGFR 相关性最好的单个基因是斯钙素 1 (STC1)。 STC1 表达还与移植时受体的大小以及 6 个月时的慢性同种异体移植物损伤指数相关。 结论 成人大小的移植物对儿童受体的功能适应与受体正常体积稳态的分子适应有关。我们的发现还表明斯钙素（STC1）在小儿肾移植的功能适应中发挥着重要作用。
BackgroundThe functional adaptation of adult-sized kidney (ASK) grafts to the recipient’s size is not completely reversible and is associated with irreversible histologic damage in the smallest recipients. The aim of the study was to unveil the molecular mechanisms underlying the functional adaptation of ASK transplants to small pediatric recipients.MethodsBecause physiologic and functional adaption of ASK in infants is seen maximally at 3 months after transplantation, we selected 21 pediatric recipients of an ASK with protocol biopsies at engraftment and 3 and 6 months, without delayed graft function or interval rejection, and we conducted whole-genome expression profiles of the renal allograft biopsies at 3 months and correlated results with subsequent absolute glomerular filtration rate (aGFR).ResultsSeven hundred twenty-four unique genes correlated significantly with aGFR (q value< 5%). Canonical pathway analysis identified overrepresentation of relevant pathways involved in regulation of tubular salt reabsorption and enzymatic pathways for organ development and hypertrophy. The single gene that correlated best with aGFR was stanniocalcin 1 (STC1). STC1 expression also correlated with the recipient’s size at the time of transplantation and the chronic allograft damage index at 6 months.ConclusionsFunctional adaptation of adult-sized grafts to the pediatric recipient is associated with molecular adaptation for normal-volume homeostasis of the recipient. Our finding also suggests that stanniocalcin (STC1) plays an important role on functional adaption in pediatric kidney transplantation.