PMID- 38409842
OWN - NLM
STAT- MEDLINE
DCOM- 20240228
LR  - 20240228
IS  - 1944-7930 (Electronic)
IS  - 1539-6509 (Linking)
VI  - 36
IP  - 181
DP  - 2024 Feb
TI  - Down-Regulation of INSR Restores Th17/Treg Immune Balance and Alleviates Airway 
      Hyperviscosity in Asthmatic Mice via Inactivation of STAT3 Pathway.
PG  - 372-384
LID - 10.24976/Discov.Med.202436181.35 [doi]
AB  - BACKGROUND: Allergic asthma (AA) is a prevalent chronic airway inflammation 
      disease. In this study, this study aims to investigate the biological functions 
      and potential regulatory mechanisms of the insulin receptor (INSR) in the 
      progression of AA. METHODS: BALB/c mice (n = 48) were randomly divided into the 
      following groups: control group, AA group, AA+Lentivirus (Lv)-vector short 
      hairpin RNA (shRNA) group, AA+Lv-vector group, AA+Lv-INSR shRNA group, and 
      AA+Lv-INSR group. The pulmonary index was calculated. mRNA and protein expression 
      levels of INSR, signal transducer and activator of transcription 3 (STAT3), Janus 
      kinase 2 (JAK2), phosphorylated-STAT3 (p-STAT3), phosphorylated-JAK2 (p-JAK2), 
      alpha-smooth muscle actin (alpha-SMA), febrile neutropenia (FN), mucin 5AC (MUC5AC), 
      and mucin 5B (MUC5B) were examined using reverse-transcription quantitative PCR 
      (RT-qPCR) and western blot assays. Positive expressions of INSR, retinoic 
      acid-related orphan receptor gamma-t (RORgammat), and forkhead box protein P3 (Foxp3) 
      were quantified by immunohistochemistry. Fluorescence intensities of alpha-SMA and FN 
      were detected by immunofluorescence. Pathological morphology was observed through 
      hematoxylin-eosin (H&E) staining, Masson staining, and Periodic Acid-Schiff (PAS) 
      staining. Contents of immunoglobulin E (IgE), interleukin-6 (IL-6), eotaxin, 
      interleukin-4 (IL-4), interleukin-13 (IL-13), interferon-gamma (IFN-gamma), 
      interleukin-17 (IL-17), and interleukin-10 (IL-10) were quantified using 
      enzyme-linked immunosorbent assay (ELISA). The percentage of T helper 17 (Th17) 
      and regulatory T (Treg) cells was determined through flow cytometry. RESULTS: 
      Compared to the control group, expression levels of INSR, p-STAT3, p-JAK2, alpha-SMA, 
      FN, MUC5AC, MUC5B, RORgammat, and Foxp3, as well as IgE, IL-6, eotaxin, IL-4, IL-13, 
      and IL-17 contents, pulmonary index, glycogen-positive area (%), and Th17 cell 
      percentage significantly increased (p < 0.05). Additionally, pulmonary 
      histopathological deterioration and collagen deposition were aggravated, while 
      Treg cell percentage and IFN-gamma and IL-10 contents remarkably decreased (p < 
      0.05). The overexpression of INSR further exacerbated the progression of allergic 
      asthma, but the down-regulation of INSR reversed the trends of the above 
      indicators. CONCLUSIONS: The down-regulation of INSR alleviates airway 
      hyperviscosity, inflammatory infiltration, and airway remodeling, restoring 
      Th17/Treg immune balance in AA mice by inactivating the STAT3 pathway.
FAU - Jin, Xuanlin
AU  - Jin X
AD  - Laboratory Medical College, Wenzhou Medical University, 325006 Wenzhou, Zhejiang, 
      China.
FAU - Wang, Jin
AU  - Wang J
AD  - Department of Pediatric, Beiyuan Community Health Service Center in Yiwu, 322000 
      Jinhua, Zhejiang, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Discov Med
JT  - Discovery medicine
JID - 101250006
RN  - 130068-27-8 (Interleukin-10)
RN  - 0 (Interleukin-17)
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (RNA, Small Interfering)
RN  - Pulmonary Disease, Chronic Obstructive, Severe Early-Onset
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Interleukin-10
MH  - Interleukin-17/genetics/metabolism
MH  - Interleukin-4/genetics/metabolism
MH  - T-Lymphocytes, Regulatory/metabolism/pathology
MH  - Interleukin-13/genetics/metabolism
MH  - Interleukin-6/metabolism
MH  - Down-Regulation
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/metabolism
MH  - Receptor, Insulin/genetics/metabolism
MH  - *Asthma/metabolism/pathology
MH  - Immunoglobulin E/genetics/metabolism
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - RNA, Small Interfering
MH  - *Pulmonary Disease, Chronic Obstructive
OTO - NOTNLM
OT  - INSR
OT  - STAT3 pathway
OT  - Th17/Treg immune balance
OT  - airway hyperviscosity
OT  - allergic asthma
EDAT- 2024/02/27 06:45
MHDA- 2024/02/28 06:45
CRDT- 2024/02/27 02:29
PHST- 2024/02/28 06:45 [medline]
PHST- 2024/02/27 06:45 [pubmed]
PHST- 2024/02/27 02:29 [entrez]
AID - 1708325321541-1224791587 [pii]
AID - 10.24976/Discov.Med.202436181.35 [doi]
PST - ppublish
SO  - Discov Med. 2024 Feb;36(181):372-384. doi: 10.24976/Discov.Med.202436181.35.