Conditional overexpression of TGF-beta1 disrupts mouse salivary gland development and function.
Conditional overexpression of TGF-beta1 disrupts mouse salivary gland development and function.
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DOI：
10.1038/labinvest.2010.5
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发表时间：
2010-04
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已知转化生长因子-β (TGF-β)信号通过影响分支形态发生、调节ECM沉积和控制免疫稳态来影响唾液腺生理。为了研究TGF-β1在唾液腺中的作用，我们建立了一种转基因小鼠（β1glo），通过Cre重组酶进行基因组重组，有条件地过表达活性TGF-β1。用MMTV（小鼠乳腺肿瘤病毒）-Cre （MC）转基因株系繁殖β1glo小鼠，该株系主要在乳腺和唾液腺分泌细胞中表达Cre重组酶。虽然大多数双阳性（β1glo/MC）幼鼠在子宫内或刚出生时死亡，但可以看到明显的唾液腺形态发生缺陷，如分支减少和间质增加。然而，存活到成年的β1glo/MC小鼠由于唾液腺纤维化和腺泡萎缩而出现了唾液分泌不足。唾液腺中TGF-β信号传导增加，Smad2磷酸化升高，同时ECM沉积增加。特别是TGF-β1异常过表达导致小鼠唾液腺功能减退，因为正常腺实质被间质纤维组织取代。这些结果进一步暗示TGF-β在涎腺慢性感染或自身免疫性疾病Sjögren综合征或头颈癌患者放射治疗中发生的涎腺炎症和纤维化病理病例中。
Transforming growth factor-β (TGF-β) signaling is known to affect salivary gland physiology by influencing branching morphogenesis, regulating ECM deposition, and controlling immune homeostasis. To study the role of TGF-β1 in the salivary gland, we created a transgenic mouse (β1glo) that conditionally over-expresses the active TGF-β1 upon genomic recombination by the Cre recombinase. The β1glo mice were bred with a MMTV (mouse mammary tumor virus)-Cre (MC) transgenic line that expresses the Cre recombinase predominantly in the secretory cells of both the mammary and salivary glands. Although most of the double positive (β1glo/MC) pups die either in utero or just after birth, clear defects in salivary gland morphogenesis could be seen such as reduced branching and increased mesenchyme. The β1glo/MC mice that survived into adulthood, however, had hyposalivation due to salivary gland fibrosis and acinar atrophy. Increased TGF-β signaling was observed in the salivary gland with elevated phosphorylation of Smad2 and a concomitant increase in ECM deposition. In particular, aberrant TGF-β1 overexpression caused salivary gland hypofunction in this mouse model because of the replacement of normal glandular parenchyma with interstitial fibrous tissue. These results further implicate TGF-β in pathological cases of salivary gland inflammation and fibrosis that occur with chronic infections in the glands or with the autoimmune disease, Sjögren’s syndrome or with the radiation therapy given to head-and-neck cancer patients.
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影响因子：
--
作者：
HARDMAN, P;SPOONER, BS
通讯作者：
SPOONER, BS
DOI：
10.1177/10454411920040010401
发表时间：
1992-01-01
期刊：
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE
影响因子：
--
作者：
BAUM, BJ;SHIP, JA;WU, AJ
通讯作者：
WU, AJ
影响因子：
3.4
作者：
Delporte, Christine;Steinfeld, Serge
通讯作者：
Steinfeld, Serge
影响因子：
3.5
作者：
Bradley, Sarah V.;Hyun, Teresa S.;Ross, Theodora S.
通讯作者：
Ross, Theodora S.
影响因子：
27.4
作者：
KOSKI, H;KONTTINEN, YT;MALMSTROM, M
通讯作者：
MALMSTROM, M