Effect of SOST gene deletion on the progression of renal interstitial fibrosis in obstructive kidney injury
Effect of SOST gene deletion on the progression of renal interstitial fibrosis in obstructive kidney injury
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SOST基因缺失对梗阻性肾损伤肾间质纤维化进展的影响
DOI：
10.3109/0886022x.2015.1077323
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发表时间：
2015
期刊：
影响因子：
3
通讯作者：
Bai Ding
中科院分区：
文献类型：
--
作者：
Wang Lu-Fei;Wu Hao;Xu Yang;Deng Meng;Han Xiang-Long;Bai Ding
摘要目的：Sost/skerostin在介导组织对损伤/炎症的纤维化反应中的作用目前尚不清楚。因此，我们进行了这项研究，首次确定Sost/skerostin在肾间质纤维化(RIF)中是否起作用。方法：采用单侧输尿管梗阻(UUO)复制梗阻性肾损伤模型。将12只雌性SOST基因敲除(SOST KO)小鼠和12只年龄匹配的野生型(WT)小鼠随机分为3组：假手术组、UUO 3 d组和UUO 7 d组，于各时间点处死小鼠，取肾组织。苏木精-伊红染色和Masson染色评价组织病理学改变，RT-PCR法和Western-Blot法检测α-平滑肌肌动蛋白(α-SMA)、I型胶原(Col-I)和纤维连接蛋白(FN)的表达。结果：假手术组WT和SOST KO均未见纤维化改变。UUO后3d，肾组织总病理评分和纤维化面积加重，α-SMA、Col-I和FN表达上调，但WT组与SOST KO组差异无统计学意义。UUO后7d，与WT组相比，SOST KO组小鼠肾组织总病理评分和纤维化面积百分比明显升高，纤维化标志物α-SMA和FN mRNA表达水平明显升高。结论：SOST基因可能参与了RIF进展的调控。在梗阻性肾损伤中，SOST基因缺失可能会增强肾脏的纤维化反应，促进RIF的进展。但还需要更多的证据来进一步确定Sost/skerostin在RIF进展中的作用。
Abstract Objectives: The role of SOST/sclerostin in mediating tissue fibrogenic response to injury/inflammation remains largely unknown. Thus, we conducted this study to determine whether SOST/sclerostin plays a role in renal interstitial fibrosis (RIF) for the first time. Methods: Unilateral ureteral obstruction (UUO) was performed to create obstructive kidney injury model. Twelvemale SOST knockout (SOST KO) mice and 12 age-matched wild-type (WT) mice were divided into three groups: sham surgery, UUO 3 d and UUO 7 d. The mice were sacrificed at each time point and kidney tissues were collected. Histopathological changes were evaluated by hematoxylin and eosin and Masson staining, while α-smooth muscle actin (α-SMA), type I collagen (Col-I) and fibronectin (FN) expression levels were detected by RT-PCR and western-blot. Results: In sham control group, neither WT nor SOST KO exhibited fibrotic change. On 3 days after UUO, total renal histopathological score and fibrotic area were aggravated and α-SMA, Col-I and FN expressions were upregulated, but no difference was observed between WT and SOST KO. On 7 days after UUO, compared with WT, SOST KO mice showed higher total renal histopathological score and fibrotic area percentage, as well as a higher level of fibrogenic marker mRNA/protein expression (except for α-SMA mRNA and FN mRNA). Conclusion: It is supposed that SOST gene is involved in the regulation of RIF progression. In obstructive kidney injury, SOST gene deletion would probably enhance renal fibrogenic response and promote the progression of RIF. But more evidences are needed to further identify the role of SOST/sclerostin in mediating RIF progression.