Universität zu Köln

Thangaratnarajah, Chansutha, Dinger, Katharina, Vohlen, Christina, Klaudt, Christian, Nawabi, Jawed, Garcia, Eva Lopez, Kwapiszewska, Grazyna, Dobner, Julia, Nuesken, Kai D., van Koningsbruggen-Rietschel, Silke, von Hoersten, Stephan, Doetsch, Joerg and Alcazar, Miguel A. Alejandre (2017). Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction. Am. J. Physiol.-Lung Cell. Mol. Physiol., 313 (3). S. L491 - 16. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1504

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Abstract

Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21,NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPK alpha signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPK alpha signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY-/-mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates 1) IL-6 and lung STAT3/AMPK alpha signaling, and 2) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thangaratnarajah, Chansutha UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Klaudt, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nawabi, Jawed UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia, Eva Lopez UNSPECIFIED UNSPECIFIED UNSPECIFIED Kwapiszewska, Grazyna UNSPECIFIED UNSPECIFIED UNSPECIFIED Dobner, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuesken, Kai D. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Koningsbruggen-Rietschel, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED von Hoersten, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-220550
DOI:	10.1152/ajplung.00432.2016
Journal or Publication Title:	Am. J. Physiol.-Lung Cell. Mol. Physiol.
Volume:	313
Number:	3
Page Range:	S. L491 - 16
Date:	2017
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1504
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYMPATHETIC-NERVE ACTIVITY; DIPEPTIDYL PEPTIDASE 4; NEUROPEPTIDE-Y; MYOFIBROBLAST DIFFERENTIATION; BRONCHOPULMONARY DYSPLASIA; BLOOD-PRESSURE; CHILDREN BORN; FETAL SHEEP; MOUSE MODEL; SCHOOL-AGE Multiple languages Physiology; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22055