Follistatin-like 1(FSTL1)是一个可以被TGF-β1诱导产生的分泌型胞外糖蛋白,它在输尿管和肾组织中都有较高表达.缺失FSTL1会导致小鼠先天性输尿管积水和肾盂积水.本研究拟建立单侧输尿管结扎(unilateral ureteral obstruction,UUO)诱导的小鼠肾间质纤维化模型,探讨FSTL1在肾间质纤维化中的表达及其在病理发生过程中的作用.小鼠右侧肾脏行UUO手术,左侧肾脏作为对照,UUO术后14d小鼠被处死.H&E和Masson染色检测肾间质纤维化程度;qRT-PCR和Western blot检测肾脏组织中纤维化特征分子,如α平滑肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原(typeⅠcollagen,COL1)和纤维连接蛋白(fibronectin,Fn),以及FSTL1的表达;免疫组化检测FSTL1表达和分布.UUO损伤的右肾组织表现出严重的间质纤维化,并且胞外基质(COL1,Fn)以及成纤维细胞活化标志物(α-SMA)的mRNA及蛋白表达水平也显著升高.同时发现,FSTL1的mRNA及蛋白表达水平在UUO损伤的右肾组织也显著升高,并且主要集中在肾小管上皮细胞中表达.因此推测,小鼠肾间质纤维化的病理过程可能与FSTL1表达上调有关,但其功能和确切作用机制还需进一步探讨.
Follistatin-like 1 (FSTL1), a TGF-βl-inducible gene, encodes a secreted extracellular glyco- protein with expression.in ureter and kidney. Deletion of Fstll in mice results in congenital hydroureter and hy- dronephrosis. The potential role of FSTL1 in unilateral ureter obstruction (UUO)-induced renal interstitial fi- brosis was investigated. UUO operation was performed on mice right-side kidneys, while their left-side pairs were used as controls. Mice were sacrificed after 14 days of UUO. H&E and Masson staining were used to ele- vate renal pathological changes, qRT-PCR and Western blot were used to detect the mRNA and protein expres- sions of a-SMA (a-smooth muscle actin), COL1 (type I collagen), Fn (fibroneetin) and FSTL1. Immunohis- tochemistry was used to detect expression and distribution of FSTL1. UUO-injured kidney tissues demonstrated severe interstitial fibrotic phenotype, accompanied by the increased mRNA and protein expressions of ECM components (COL1, Fn) and activated fibroblast marker (a-SMA). Meanwhile, the mRNA and protein expres- sions of FSTL1 were also increased in UUO-injured kidney tissues. We also observed considerably increased FSTL1 staining in renal tubule epithelial cells. Taken together, those observations show that FSTL1 is associ- ated with the pathological process of mice renal interstitial fibrogenesis.