Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats.
Characterisation of the proximal airway squamous metaplasia induced by chronic tobacco smoke exposure in spontaneously hypertensive rats.
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DOI：
10.1186/1465-9921-10-118
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发表时间：
2009-11-24
影响因子：
5.8
通讯作者：
Pinkerton KE
中科院分区：
文献类型：
--
作者：
Bolton SJ;Pinnion K;Oreffo V;Foster M;Pinkerton KE
持续暴露于烟草烟雾(TS)是慢性阻塞性肺疾病(COPD)的关键原因，COPD是一种复杂的多因素疾病，很难在啮齿动物身上建立模型。自发性高血压(SH)大鼠表现出几种与COPD相关的共病，如高血压和凝血功能增强。我们已经研究了SH大鼠是否是COPD更合适的动物范例。用TS染毒SH大鼠14周，每天染毒6h，每周染毒3d，取肺组织进行免疫组织化学检测。TS诱导近端呼吸道CK13阳性鳞状化生，Ki67和P63也染色。我们假设这种损害是由基底细胞增殖引起的，这种细胞分化为鳞状细胞表型。功能标记CC10和表面活性物质D的染色图谱的差异，而不是磷酸化p38的染色图谱，表明失去了作为分泌细胞的适当功能。在实质内，CC10和表面活性物质D的染色图谱也不同，这表明可能试图补偿近端呼吸道的损失。在人类COPD切片中，CK13阳性的鳞状化生区域显示零星的P63染色，这表明与大鼠不同，这不是基底细胞驱动的病变。这项研究表明，虽然大鼠和人的近端呼吸道上皮化生都是CK13+，因此是鳞状的，但它们可能由不同的机制引起。
Continuous exposure to tobacco smoke (TS) is a key cause of chronic obstructive pulmonary disease (COPD), a complex multifactorial disease that is difficult to model in rodents. The spontaneously hypertensive (SH) rat exhibits several COPD-associated co-morbidities such as hypertension and increased coagulation. We have investigated whether SH rats are a more appropriate animal paradigm of COPD. SH rats were exposed to TS for 6 hours/day, 3 days/week for 14 weeks, and the lung tissues examined by immunohistochemistry. TS induced a CK13-positive squamous metaplasia in proximal airways, which also stained for Ki67 and p63. We hypothesise that this lesion arises by basal cell proliferation, which differentiates to a squamous cell phenotype. Differences in staining profiles for the functional markers CC10 and surfactant D, but not phospho-p38, indicated loss of ability to function appropriately as secretory cells. Within the parenchyma, there were also differences in the staining profiles for CC10 and surfactant D, indicating a possible attempt to compensate for losses in proximal airways. In human COPD sections, areas of CK13-positive squamous metaplasia showed sporadic p63 staining, suggesting that unlike the rat, this is not a basal cell-driven lesion. This study demonstrates that although proximal airway metaplasia in rat and human are both CK13+ and therefore squamous, they potentially arise by different mechanisms.
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影响因子：
5
作者：
Chilosi, M;Poletti, V;Doglioni, C
通讯作者：
Doglioni, C
影响因子：
2.9
作者：
BROERS, JLV;DELEIJ, L;RAMAEKERS, FCS
通讯作者：
RAMAEKERS, FCS
影响因子：
5.8
作者：
Lapperre TS;Sont JK;van Schadewijk A;Gosman MM;Postma DS;Bajema IM;Timens W;Mauad T;Hiemstra PS;GLUCOLD Study Group
通讯作者：
GLUCOLD Study Group
影响因子：
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作者：
Hong, KU;Reynolds, SD;Stripp, BR
通讯作者：
Stripp, BR
影响因子：
15.9
作者：
Araya, Jun;Cambier, Stephanie;Nishimura, Stephen L.
通讯作者：
Nishimura, Stephen L.