生物谷報道：美國科學家近日研究發(fā)現(xiàn),，激活一個重要的分子路徑能夠增加肺干細胞,。這一發(fā)現(xiàn)有助于開發(fā)相關治療方案以進行傷后或病后肺部組織的修復。相關論文發(fā)表在《自然—遺傳學》（Nature Genetics）上,。
美國賓夕法尼亞大學醫(yī)學院的Edward Morrisey和同事研究發(fā)現(xiàn),，激活Wnt信號路徑能夠增加細支氣管肺泡干細胞（bronchioalveolar stem cells）的數(shù)量。一種名為GATA6的蛋白能夠抑制Wnt路徑,，方式是通過直接調(diào)控Wnt路徑中另一種名為Fzd2的蛋白的表達,。
Wnt路徑是干細胞生物學中一個主要的路徑。GATA6負調(diào)控Wnt路徑并且其已被證明在胚胎干細胞復制和分化中也起重要作用,，這表明這兩種路徑相關聯(lián)的地方不限于肺干細胞,，它們在心臟、腸道以及胰腺等組織中也發(fā)揮著重要作用,。
Wnt路徑可用鋰等物質(zhì)進行藥理學調(diào)控,，應用這些物質(zhì)可以使肺部或其它組織中的關鍵干細胞群進行強制性擴張和分化，以對成熟組織進行傷后或病后修復,。
Morrisey實驗室今后將對Wnt路徑對肺部及其它組織中的成熟組織修復進行更廣泛的基礎性研究,，同時也將開始確定對這條路徑的藥理學激活或抑制是否真的可以用于治療。（生物谷www.bioon.com）
生物谷推薦原始出處：
Nature Genetics,，doi:10.1038/ng.157,，Yuzhen Zhang，Edward E Morrisey
A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration
Yuzhen Zhang1, Ashley M Goss2, Ethan David Cohen1, Rachel Kadzik2, John J Lepore1, Karthika Muthukumaraswamy1, Jifu Yang1, Francesco J DeMayo3, Jeffrey A Whitsett4, Michael S Parmacek1,5,6 & Edward E Morrisey1,2,5,6
Abstract
Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased -catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.
