Spontaneous acinar and ductal regrowth after meibomian gland atrophy induced by deletion of FGFR2 in a mouse model.
Spontaneous acinar and ductal regrowth after meibomian gland atrophy induced by deletion of FGFR2 in a mouse model.
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DOI：
10.1016/j.jtos.2021.11.005
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发表时间：
2022-10
期刊：
影响因子：
6.4
通讯作者：
Reneker, Lixing W.
中科院分区：
文献类型：
--
作者：
Yang, Xiaowei;Zhong, Xingwu;Huang, Andrew J. W.;Reneker, Lixing W.
我们已经证明，成纤维细胞生长因子受体2基因（Fgfr 2）的缺失导致睑板腺（MG）萎缩的诱导条件敲除小鼠模型，称为Fgfr 2CKO。在此，我们研究了MG在该模型中萎缩后是否自发恢复。将两个月大的Fgfr 2CKO小鼠以80 μg/gm体重腹膜注射一次或两次多西环素（Dox）以通过Fgfr 2缺失诱导各种严重程度的MG萎缩。腺泡和导管组织的恢复通过睑板造影、脂质染色和角蛋白-6a的免疫荧光进行监测。腺泡和导管分化和增殖的生物标志物也通过免疫染色进行了检查。在Fgfr 2CKO小鼠中单次注射Dox引起重度腺泡和中度导管萎缩。在第二次注射Dox后发生了严重的导管缩短或损失，推测与报告的导管上皮细胞循环较慢有关。在两种注射方案中，在60天的时间内观察到萎缩后的自发腺泡再生长。然而，在两次注射Fgfr 2CKO小鼠中，不太稳健的腺泡恢复与更多的导管结构破坏相关。我们目前的研究结果进一步证实了FGFR 2在MG体内平衡中的作用，并表明FGFR 2信号传导可能为人类年龄相关MG功能障碍的腺泡再生提供了一种潜在的策略。我们的数据表明，自发性MG恢复取决于导管萎缩的程度，这表明导管上皮细胞可能为腺泡再生提供祖细胞。然而，导管组织作为腺泡祖细胞来源的作用有待进一步研究。
We have demonstrated that deletion of fibroblast growth factor receptor 2 gene (Fgfr2) leads to Meibomian gland (MG) atrophy in an inducible conditional knockout mouse model, referred as Fgfr2CKO. Herein, we investigated whether MG spontaneously recovers after atrophy in this model. Two months old Fgfr2CKO mice were injected peritoneally once or twice of doxycycline (Dox) at 80 μg/gm of body weight to induce MG atrophy of various severities via Fgfr2 deletion. Recovery of acinar and ductal tissues was monitored by meibography, lipid staining and immunofluorescence against keratin-6a in MG whole-mount. Biomarkers for acinar and ductal differentiation and proliferation were also examined by immunostaining. Single Dox injection in Fgfr2CKO mice caused severe acinar and moderate ductal atrophy. Severe ductal shortening or loss occurred after second Dox injection, presumably related to the reported slower cycling of the ductal epithelia. Spontaneous acinar regrowth after atrophy was observed over a period of 60 days in both injection regimens. However, less robust acinar recovery was associated with more disrupted ductal structures in twice injected Fgfr2CKO mice. Our current findings further substantiate the role of FGFR2 in MG homeostasis, and suggest that FGFR2-signaling may provide a potential strategy for regenerating acini from age-related MG dysfunction in humans. Our data demonstrated that spontaneous MG recovery depends on the extent of ductal atrophy, suggesting that ductal epithelia may provide the progenitor cells for acinar regeneration. Nonetheless, the role of ductal tissue as the source of acinar progenitors awaits further investigation.
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DOI：
10.1136/bjophthalmol-2014-305220
发表时间：
2014-12
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Bilkhu PS;Naroo SA;Wolffsohn JS
通讯作者：
Wolffsohn JS
影响因子：
2.1
作者：
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通讯作者：
Pe'er, J
影响因子：
2.8
作者：
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Shimazaki, Jun
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DOI：
10.1136/bjophthalmol-2012-302668
发表时间：
2013-06
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Arita R;Suehiro J;Haraguchi T;Maeda S;Maeda K;Tokoro H;Amano S
通讯作者：
Amano S
影响因子：
11.4
作者：
Grose, Richard;Fantl, Vera;Dickson, Clive
通讯作者：
Dickson, Clive