PMID- 28325283
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 6
DP  - 2017 Mar 17
TI  - Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis 
      Development.
PG  - 163-172
LID - S2162-2531(16)30376-6 [pii]
LID - 10.1016/j.omtn.2016.12.008 [doi]
AB  - Pulmonary fibrosis is a progressive lung disorder characterized by interstitial 
      fibrosis, for which no effective treatments are available. Chondroitin sulfate 
      proteoglycan (CSPG) has been shown to be a mediator, but the specific component 
      of glycosaminoglycan chains of CSPG has not been explored. We show that 
      chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering 
      RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to 
      inhibit CHST15 mRNA and its product, CS-E. CS-E augments cell contraction and 
      CHST15 siRNA inhibits collagen production. We found that bleomycin treatment 
      increased CHST15 expression in interstitial fibroblasts at day 14. CHST15 siRNA 
      was injected intranasally on days 1, 4, 8, and 11, and CHST15 mRNA was 
      significantly suppressed by day 14. CHST15 siRNA reduced lung CSPG and the grade 
      of fibrosis. CHST15 siRNA repressed the activation of fibroblasts, as evidenced 
      by suppressed expression of alpha smooth muscle actin (alphaSMA), connective tissue 
      growth factor (CTGF), lysyl oxidase like 2 (LOXL2), and CC-chemokine ligand 2 
      (CCL2)/monocyte chemoattractant protein-1 (MCP-1). Inflammatory infiltrates in 
      the bronchoalveolar lavage fluid (BALF) and interstitium were diminished 
      by CHST15 siRNA. These results indicate a pivotal role for CHST15 in 
      fibroblast-mediated lung fibrosis and suggest a possible new therapeutic role for 
      CHST15 siRNA in pulmonary fibrosis.
CI  - Copyright (c) 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Kai, Yoshiro
AU  - Kai Y
AD  - Second Department of Internal Medicine, Nara Medical University, Nara 634-8522, 
      Japan. Electronic address: y-kai@eco.ocn.ne.jp.
FAU - Tomoda, Koichi
AU  - Tomoda K
AD  - Second Department of Internal Medicine, Nara Medical University, Nara 634-8522, 
      Japan.
FAU - Yoneyama, Hiroyuki
AU  - Yoneyama H
AD  - Stelic Institute and Co. Inc., Tokyo 106-0044, Japan.
FAU - Kitabatake, Masahiro
AU  - Kitabatake M
AD  - Department of Immunology, Nara Medical University, Nara 634-8522, Japan.
FAU - Nakamura, Atsuhiro
AU  - Nakamura A
AD  - Second Department of Internal Medicine, Nara Medical University, Nara 634-8522, 
      Japan.
FAU - Ito, Toshihiro
AU  - Ito T
AD  - Department of Immunology, Nara Medical University, Nara 634-8522, Japan.
FAU - Yoshikawa, Masanori
AU  - Yoshikawa M
AD  - Second Department of Internal Medicine, Nara Medical University, Nara 634-8522, 
      Japan.
FAU - Kimura, Hiroshi
AU  - Kimura H
AD  - Second Department of Internal Medicine, Nara Medical University, Nara 634-8522, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20161231
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC5363499
OTO - NOTNLM
OT  - bleomycin
OT  - chondroitin sulfate
OT  - chondroitin sulfate proteoglycans
OT  - fibroblasts
OT  - idiopathic pulmonary fibrosis
OT  - macrophages
OT  - pulmonary fibrosis
EDAT- 2017/03/23 06:00
MHDA- 2017/03/23 06:01
PMCR- 2016/12/31
CRDT- 2017/03/23 06:00
PHST- 2016/09/06 00:00 [received]
PHST- 2016/12/20 00:00 [revised]
PHST- 2016/12/20 00:00 [accepted]
PHST- 2017/03/23 06:00 [entrez]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/03/23 06:01 [medline]
PHST- 2016/12/31 00:00 [pmc-release]
AID - S2162-2531(16)30376-6 [pii]
AID - 10.1016/j.omtn.2016.12.008 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2017 Mar 17;6:163-172. doi: 10.1016/j.omtn.2016.12.008. 
      Epub 2016 Dec 31.