PMID- 33609775 OWN - NLM STAT- MEDLINE DCOM- 20211117 LR - 20211117 IS - 1878-1519 (Electronic) IS - 1569-9048 (Linking) VI - 288 DP - 2021 Jun TI - SerpinA3n affects ovalbumin (OVA)-induced asthma in neonatal mice via the regulation of collagen deposition and inflammatory response. PG - 103642 LID - S1569-9048(21)00027-6 [pii] LID - 10.1016/j.resp.2021.103642 [doi] AB - OBJECTIVE: To investigate the effects of serine protease inhibitor 3n (SerpinA3n) in a neonatal mouse model of asthma. METHODS: The study utilized a neonatal mouse ovalbumin (OVA) sensitization model of asthma. Wild type (WT) and SerpinA3n(-/-) mice were randomly divided into WT/SerpinA3n(-/-) + saline, WT/SerpinA3n(-/-) + OVA, WT/SerpinA3n(-/-) + OVA + rSerpinA3n (recombinant mouse SerpinA3n protein), and WT/SerpinA3n(-/-) + OVA + DEX (dexamethasone, positive control) groups followed by hematoxylin-eosin (HE) staining, Masson's trichrome stainings, Sircol soluble collagen assay, quantitative real time polymerase chain reaction (qRT-PCR), Western Blot and enzyme linked immunosorbent assay (ELISA). RESULTS: OVA-induced neonatal mice showed the increases in airway hyper-reactivity with the up-regulated total cells, eosinophil, lymphocyte and neutrophil in bronchoalveolar lavage fluid (BALF), which was much higher in WT + OVA + rSerpinA3n group (P < 0.05). SerpinA3n(-/-) suppressed the serum concentrations of total immunoglobulin E (IgE) and OVA-specific IgG1 in OVA-induced asthmatic mice, and alleviated the pathological changes of lung tissues, which was reversed by rSerpinA3n injection (P < 0.05). Besides, WT + OVA group showed more severe in collagen deposition in lung tissues than SerpinA3n(-/-) + OVA group with increased expression of matrix metallopeptidase-2 (MMP-2), MMP-9, Eotaxin-1, Interleukin 5 (IL-5), IL-13 and IL-4 in lung tissues and deceased IL-10 and Interferon-gamma (IFN-gamma) (P < 0.05). Nevertheless, the ameliorating effects of SerpinA3n knockout on OVA-induced asthmatic mice can be reversed by rSerpinA3n. CONCLUSION: SerpinA3n knockout can attenuate airway hyper-reactivity, mitigate inflammatory responses and reduce collagen deposition in lung tissues of neonatal mice with asthma. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Zhang, Hai-Tao AU - Zhang HT AD - Department of Pediatrics, The People's Hospital of Shouguang, Shouguang, 262700, Shandong, China. FAU - Wang, Ping AU - Wang P AD - Department of Pediatrics, The People's Hospital of Shouguang, Shouguang, 262700, Shandong, China. FAU - Li, Yuan AU - Li Y AD - Department of Pediatrics, The People's Hospital of Shouguang, Shouguang, 262700, Shandong, China. FAU - Bao, Yong-Bo AU - Bao YB AD - Department of Pediatrics, Zaozhuang Municipal Hospital, Zaozhuang, 277100, Shandong, China. Electronic address: zhmm77@163.com. LA - eng PT - Journal Article DEP - 20210217 PL - Netherlands TA - Respir Physiol Neurobiol JT - Respiratory physiology & neurobiology JID - 101140022 RN - 0 (Acute-Phase Proteins) RN - 0 (Serpina3n protein, mouse) RN - 0 (Serpins) RN - 9006-59-1 (Ovalbumin) RN - 9007-34-5 (Collagen) SB - IM MH - Acute-Phase Proteins/*metabolism MH - Animals MH - Animals, Newborn MH - Asthma/blood/chemically induced/immunology/*metabolism MH - Collagen/*metabolism MH - Disease Models, Animal MH - Female MH - Inflammation/blood/immunology/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Ovalbumin/*pharmacology MH - Serpins/*metabolism OTO - NOTNLM OT - Asthma OT - Collagen deposition OT - Gene knockout OT - Inflammatory response OT - SerpinA3n EDAT- 2021/02/21 06:00 MHDA- 2021/11/18 06:00 CRDT- 2021/02/20 20:10 PHST- 2020/11/30 00:00 [received] PHST- 2021/02/07 00:00 [revised] PHST- 2021/02/13 00:00 [accepted] PHST- 2021/02/21 06:00 [pubmed] PHST- 2021/11/18 06:00 [medline] PHST- 2021/02/20 20:10 [entrez] AID - S1569-9048(21)00027-6 [pii] AID - 10.1016/j.resp.2021.103642 [doi] PST - ppublish SO - Respir Physiol Neurobiol. 2021 Jun;288:103642. doi: 10.1016/j.resp.2021.103642. Epub 2021 Feb 17.