Identification and importance of hyaluronan and proteoglycan link protein 1 in developing mouse lungs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Saitama Medical University
• Principal Investigator: Fumihiko Namba 埼玉医科大学, 医学部, 准教授 (20643323)
• Research Collaborator: TANAKA kosuke ; MATSUOKA kikumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 高濃度酸素 / 新生児 / ヒアルロン酸プロテオグリカン結合蛋白質1 / マウス / 遺伝子発現解析 / マイクロアレイ

Outline of Final Research Achievements

In premature infants, the lungs may not develop fully and have limited diffusing capacity for gas exchange; hence, supplemental oxygen is required. As excessive oxygen is known to be toxic to the lungs. Our objectives were to identify a novel biomarker in neonatal mouse lungs exposed to hyperoxia using microarrays for gene expression profiling and to evaluate its importance in the developing mouse lungs.
We identified HAPLN1 as a candidate gene that had significantly increased or decreased expression levels in hyperoxia-exposed mice compared with that in controls at 7 days. HAPLN1 knockout (KO) newborn mice died shortly after birth. The lungs displayed decreased lung weight, decreased lung wet/dry weight ratio, reduced airspace, increased HA content, and increased collagen content, in HAPLN1 KO embryos at E18.5 compared with those in wild-type mice. HAPLN1 might play an important role in morphogenesis in developing mouse lungs by organizing the components of extracellular matrix.

Free Research Field

新生児科学

Academic Significance and Societal Importance of the Research Achievements

新生児慢性肺疾患は早産・低出生体重児の重篤な呼吸器疾患であり、現在有効な治療法がなく、長期的な呼吸器及び神経学的合併症を残す。今回、新生児慢性肺疾患動物モデルを用いて、同疾患の重症化に関与する可能性のある細胞外基質蛋白質であるヒアルロン酸プロテオグリカン結合蛋白質1の遺伝子発現上昇を見出し、同蛋白質が胎児・新生児期の肺発達に重要な役割を果たすことをヒアルロン酸プロテオグリカン結合蛋白質1欠損マウスを用いて証明した。以上のことから、同蛋白質が新生児慢性肺疾患の新規バイオマーカーおよび新規治療ターゲットになることが示唆された。