Phoenix Children's Research Institute Study Identifies FOXF1 Enhancers Involved in Rare Lung Disease
Phoenix Children's Research Institute Study Identifies FOXF1 Enhancers Involved in Rare Lung Disease
Research has implications for more common pulmonary disorders
該研究對更常見的肺部疾病具有重要意義
PHOENIX, June 19, 2024 /PRNewswire/ -- According to a study published in Nature Communications, research conducted at the Phoenix Children's Research Institute at the University of Arizona College of Medicine — Phoenix, shows how frequent non-coding FOXF1 gene deletions that interfere with important DNA regulatory regions, called enhancers, can lead to Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV), a rare, lethal, genetic lung disease which causes respiratory failure in newborns and infants.
2024年6月19日，鳳凰城 / PRNewswire——根據發表在《自然通訊》上的一項研究，亞利桑那大學醫藥學院鳳凰城分校鳳凰城兒童研究所的研究表明，頻繁的非編碼基因FOXF1基因缺失干擾了重要的DNA調節區域——增強子，可以導致肺泡毛細血管錯位性發育不良（ACDMPV），一種罕見的致命的遺傳性肺病，導致新生兒和嬰兒的呼吸衰竭。FOXF1基因的缺失干擾了重要的DNA調節區域增強子，可以導致肺泡毛細血管錯位性發育不良（ACDMPV），這是一種罕見的致命遺傳性肺病，會導致新生兒和嬰兒的呼吸衰竭。
The FOXF1 protein is critically important in pulmonary vascular development, specifically responsible for the extension and branching of airways and blood vessels in the developing lung.
FOXF1蛋白在肺血管發育中至關重要，負責發育中肺部空氣管和血管的延伸和分支。
"Prior to this study, we knew deletions and mutations in the FOXF1 gene locus can result in ACDMPV, so our goal was to identify FOXF1 enhancers associated with the disease so we can diagnose it more precisely in newborn babies," said Vlad Kalinichenko, MD, PhD, internationally renowned lung development and regeneration researcher and director of the Phoenix Children's Research Institute at the University of Arizona College of Medicine – Phoenix.
“在這項研究之前，我們知道FOXF1基因座上的缺失和突變可能導致ACDMPV，因此我們的目標是識別與該疾病有關的FOXF1增強子，以便我們可以更精確地診斷新生兒，”Vlad Kalinichenko博士說。他是國際知名的肺部發育和再生研究人員，也是亞利桑那大學醫學院鳳凰城分校鳳凰城兒童研究所的主任。FOXF1“在這項研究中，我們與辛辛那提兒童醫院醫學中心合作，確定了FOXF1基因座中的四個上游增強子，即FOXF1在肺部1、2、3和4中的表達。它進一步表明，這些元素刺激了肺內皮細胞和基質細胞（如成纖維細胞和外周細胞）的細胞特異性FOXF1表達。肺內皮細胞對肺泡的發育至關重要，肺泡是肺部氣管的微小分支，負責在血液中進行氧氣和二氧化碳的交換。同樣，肺基質細胞對肺的發育也很重要，是整體肺結構的重要組成部分。”
This study, conducted in collaboration with Cincinnati Children's Hospital Medical Center, identified four upstream enhancers in the FOXF1 gene locus — FOXF1 Expression in the Lung 1, 2, 3 and 4. It further showed these elements stimulate cell-specific FOXF1 expression in pulmonary endothelium and stromal cells, such as fibroblasts and pericytes. Pulmonary endothelial cells are essential to the development of alveoli, the tiny branches of air tubes in the lungs responsible for the exchange of oxygen and carbon dioxide in the bloodstream. Likewise, pulmonary stromal cells are also important to lung development and are a crucial component of overall lung structure.
本研究與辛辛那提兒童醫院醫學中心合作，確定了FOXF1基因座中的四個上游增強子，即FOXF1在肺部1、2、3和4中的表達。FOXF1—— FOXF1基因在肺中的表達1、2、3和4。FOXF1這進一步表明，這些元素刺激了肺內皮細胞和基質細胞（如成纖維細胞和外周細胞）的細胞特異性FOXF1表達。FOXF1肺內皮細胞對肺泡的發育至關重要，肺泡是肺部氣管的微小分支，負責在血液中進行氧氣和二氧化碳的交換。同樣，肺基質細胞對肺的發育也很重要，是整體肺結構的重要組成部分。
Since many non-coding deletions in or near the FOXF1 gene locus cause ACDMPV, identifying specific pathogenic FOXF1 enhancers — that are critical for lung development — is important to understand and diagnose ACDMPV. This work could also enable better genetic screening for the disease, which currently relies primarily on exome DNA sequencing.
由於許多與FOXF1基因座相關的非編碼基因缺失會導致ACDMPV，因此確定特定的與肺部發育關鍵的FOXF1致病性增強子對了解和診斷ACDMPV很重要。該研究還可能有助於更好地進行該病的基因篩查，目前主要依靠外顯子DNA測序。FOXF1由於許多與FOXF1基因座相關的非編碼基因缺失會導致ACDMPV，因此確定特定的與肺部發育關鍵的FOXF1致病性增強子對了解和診斷ACDMPV很重要。該研究還可能有助於更好地進行該病的基因篩查，目前主要依靠外顯子DNA測序。
"This study demonstrates four specific FOXF1 enhancers play critical roles in the development of ACDMPV and resolves an important clinical question regarding why frequent non-coding FOXF1 deletions that interfere with endothelial and mesenchymal enhancers can lead to this lethal disease," said Dr. Kalinichenko. "Identifying mutations in the FOXF1 gene locus sooner will be critical for accurate genetic diagnosis of this severe congenital disease. As we continue to gain additional insight into how genes work, it will improve our capabilities to implement effective therapeutic interventions in more common pulmonary disorders of newborns and infants, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia."
該研究證明了四種特定的FOXF1增強子可以刺激肺內的特定細胞類型FOXF1表達，是肺泡發育的關鍵組成部分。這些增強子可能有助於更好地理解和診斷ACDMPV，並實現更好地基因篩查。FOXF1 增強子在ACDMPV的發展中起到至關重要的作用，並解決了一個重要的臨床問題：爲什麼頻繁出現非編碼FOXF1縮短並干擾內皮和間充質增強子會導致這種致命疾病。卡琳尼琴科博士稱：“儘早確定FOXF1基因突變將對這種嚴重的先天性疾病的準確基因診斷關鍵。隨着我們不斷加深對基因作用方式的認識，它將改善我們針對新生兒和嬰兒更常見的肺部疾病（如支氣管肺發育不全和先天性膈疝）實施有效治療干預的能力。FOXF1干擾內皮和間充質增強子的FOXF1缺失可導致這種致命性疾病，這是一個重要的臨床問題。卡林尼琴科博士表示：“儘早確定FOXF1基因突變將對這種嚴重的先天性疾病的準確基因診斷關鍵。隨着我們不斷加深對基因作用方式的認識，它將改善我們針對新生兒和嬰兒更常見的肺部疾病（如支氣管肺發育不全和先天性膈疝）實施有效治療干預的能力。FOXF1爲提高我們針對新生兒和嬰兒更常見的肺部疾病（如支氣管肺發育不全和先天性膈疝）實施有效治療干預的能力，我們需要儘早確認FOXF1基因定位的變異情況。菲尼克斯兒童研究所在阿利桑那大學醫學院-鳳凰城分校成立於2023年5月，正式確定了醫療系統和阿利桑那大學醫學院-鳳凰城分校之間長期的研究合作。研究所包括700多項活動研究，640名研究調查員，90名研究人員，包括研究科學家，助理，生物統計學家，藥劑師，護士和協調員。科學家在包括腫瘤學、神經學、心臟病學、肺病學等多個臨床學科中從事研究。
The Phoenix Children's Research Institute at the University of Arizona College of Medicine –Phoenix launched in May 2023, formalizing a longstanding research collaboration between the health system and the University of Arizona College of Medicine – Phoenix. The Research Institute includes more than 700 active studies, 640 research investigators and 90 research staff members, including research scientists, associates, biostatisticians, pharmacists, nurses and coordinators. Scientists engage in research across multiple clinical disciplines, including cancer, neurology, cardiology, pulmonology and more.
菲尼克斯兒童醫院是全國最大的兒科保健系統之一，提供世界一流的住院治療、門診治療、創傷、急診和緊急醫療護理。醫療系統由菲尼克斯兒童醫院-托馬斯校區、菲尼克斯兒童醫院-東谷校區、菲尼克斯兒童醫院-阿翁代爾校區、菲尼克斯兒童醫院-箭頭校區、四個兒童專科及急診中心、12個社區兒科診所、20個門診診所、兩個門診手術中心以及亞利桑那州各地的七個社區服務門診診所組成。醫療系統爲兒童和家庭提供服務已經40年曆史了。菲尼克斯兒童護理網絡包括超過1175名兒科初級保健提供者和專家，在75多個亞專業領域提供醫療護理。我們與同事、合作者和社區一起，不斷提高兒科醫療、教育和創新水平，以便實現更健康的成長。欲了解更多信息，請訪問phoenixchildrens.org。
About Phoenix Children's
Phoenix Children's is one of the nation's largest pediatric health systems. It comprises Phoenix Children's Hospital – Thomas Campus, Phoenix Children's Hospital – East Valley Campus, Phoenix Children's – Avondale Campus, Phoenix Children's – Arrowhead Campus, four pediatric specialty and urgent care centers, 12 community pediatric practices, 20 outpatient clinics, two ambulatory surgery centers and seven community-service outpatient clinics throughout the state of Arizona. The system provides world-class inpatient, outpatient, trauma, emergency and urgent care, and has been serving children and families for 40 years. Phoenix Children's Care Network includes more than 1,175 pediatric primary care providers and specialists who deliver care across more than 75 subspecialties. Alongside our colleagues, collaborators and communities, we're elevating pediatric care, education and innovation, so we can all grow healthier together. For more information, visit phoenixchildrens.org.
菲尼克斯兒童醫院是全國最大的兒科保健系統之一。
菲尼克斯兒童菲尼克斯兒童醫院是全國最大的兒科保健系統之一，提供世界一流的住院治療、門診治療、創傷、急診和緊急醫療護理。醫療系統由菲尼克斯兒童醫院-托馬斯校區、菲尼克斯兒童醫院-東谷校區、菲尼克斯兒童醫院-阿翁代爾校區、菲尼克斯兒童醫院-箭頭校區、四個兒童專科及急診中心、12個社區兒科診所、20個門診診所、兩個門診手術中心以及亞利桑那州各地的七個社區服務門診診所組成。醫療系統爲兒童和家庭提供服務已經40年曆史了。欲了解更多信息，請訪問phoenixchildrens.org。
SOURCE Phoenix Children's
來源：菲尼克斯兒童
譯文內容由第三人軟體翻譯。