PMID- 28982738
OWN - NLM
STAT- MEDLINE
DCOM- 20190110
LR  - 20201209
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 314
IP  - 1
DP  - 2018 Jan 1
TI  - Intranasal administration of recombinant progranulin inhibits bronchial smooth 
      muscle hyperresponsiveness in mouse allergic asthma.
PG  - L215-L223
LID - 10.1152/ajplung.00575.2016 [doi]
AB  - Progranulin (PGRN) is a growth factor with multiple biological functions and has 
      been suggested as an endogenous inhibitor of Tumor necrosis factor-alpha 
      (TNF-alpha)-mediated signaling. TNF-alpha is believed to be one of the important 
      mediators of the pathogenesis of asthma, including airway hyperresponsiveness 
      (AHR). In the present study, effects of recombinant PGRN on TNF-alpha-mediated 
      signaling and antigen-induced hypercontractility were examined in bronchial 
      smooth muscles (BSMs) both in vitro and in vivo. Cultured human BSM cells 
      (hBSMCs) and male BALB/c mice were used. The mice were sensitized and repeatedly 
      challenged with ovalbumin antigen. Animals also received intranasal 
      administrations of recombinant PGRN into the airways 1 h before each antigen 
      inhalation. In hBSMCs, PGRN inhibited both the degradation of IkappaB-alpha (an index of 
      NF-kappaB activation) and the upregulation of RhoA (a contractile 
      machinery-associated protein that contributes to the BSM hyperresponsiveness) 
      induced by TNF-alpha, indicating that PGRN has an ability to inhibit TNF-alpha-mediated 
      signaling also in the BSM cells. In BSMs of the repeatedly antigen-challenged 
      mice, an augmented contractile responsiveness to acetylcholine with an 
      upregulation of RhoA was observed: both the events were ameliorated by 
      pretreatments with PGRN intranasally. Interestingly, a significant decrease in 
      PGRN expression was found in the airways of the repeatedly antigen-challenged 
      mice rather than those of control animals. In conclusion, exogenously applied 
      PGRN into the airways ameliorated the antigen-induced BSM hyperresponsiveness, 
      probably by blocking TNF-alpha-mediated response. Increasing PGRN levels might be a 
      promising therapeutic for AHR in allergic asthma.
FAU - Chiba, Yoshihiko
AU  - Chiba Y
AD  - Department of Physiology and Molecular Sciences, Hoshi University , Tokyo , 
      Japan.
AD  - Department of Biology, Hoshi University , Tokyo , Japan.
FAU - Danno, Shunta
AU  - Danno S
AD  - Department of Biology, Hoshi University , Tokyo , Japan.
FAU - Suto, Rena
AU  - Suto R
AD  - Department of Biology, Hoshi University , Tokyo , Japan.
FAU - Suto, Wataru
AU  - Suto W
AD  - Department of Physiology and Molecular Sciences, Hoshi University , Tokyo , 
      Japan.
FAU - Yamane, Yamato
AU  - Yamane Y
AD  - Department of Physiology and Molecular Sciences, Hoshi University , Tokyo , 
      Japan.
FAU - Hanazaki, Motohiko
AU  - Hanazaki M
AD  - Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School 
      , Kurashiki , Japan.
FAU - Katayama, Hiroshi
AU  - Katayama H
AD  - Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School 
      , Kurashiki , Japan.
FAU - Sakai, Hiroyasu
AU  - Sakai H
AD  - Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University , 
      Tokyo , Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171005
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Granulins)
RN  - 0 (Grn protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Progranulins)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Asthma/*physiopathology
MH  - Bronchi/*physiopathology
MH  - Bronchial Hyperreactivity/etiology/metabolism/*prevention & control
MH  - Cells, Cultured
MH  - Granulins
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*administration & dosage
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Smooth/metabolism/*pathology
MH  - Progranulins
MH  - Recombinant Proteins/*administration & dosage
MH  - Respiratory Hypersensitivity/etiology/metabolism/*prevention & control
MH  - Signal Transduction
OTO - NOTNLM
OT  - airway hyperresponsiveness
OT  - asthma
OT  - bronchial smooth muscle
OT  - progranulin (PGRN)
OT  - tumor necrosis factor-alpha (TNF-alpha)
EDAT- 2017/10/07 06:00
MHDA- 2019/01/11 06:00
CRDT- 2017/10/07 06:00
PHST- 2017/10/07 06:00 [pubmed]
PHST- 2019/01/11 06:00 [medline]
PHST- 2017/10/07 06:00 [entrez]
AID - ajplung.00575.2016 [pii]
AID - 10.1152/ajplung.00575.2016 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L215-L223. doi: 
      10.1152/ajplung.00575.2016. Epub 2017 Oct 5.