PMID- 31701076
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2471-254X (Electronic)
IS  - 2471-254X (Linking)
VI  - 3
IP  - 11
DP  - 2019 Nov
TI  - Liver Glycogen Phosphorylase Deficiency Leads to Profibrogenic Phenotype in a 
      Murine Model of Glycogen Storage Disease Type VI.
PG  - 1544-1555
LID - 10.1002/hep4.1426 [doi]
AB  - Mutations in the liver glycogen phosphorylase (Pygl) gene are associated with the 
      diagnosis of glycogen storage disease type VI (GSD-VI). To understand the 
      pathogenesis of GSD-VI, we generated a mouse model with Pygl deficiency (Pygl 
      (-/-)). Pygl (-/-) mice exhibit hepatomegaly, excessive hepatic glycogen 
      accumulation, and low hepatic free glucose along with lower fasting blood glucose 
      levels and elevated blood ketone bodies. Hepatic glycogen accumulation in Pygl 
      (-/-) mice increases with age. Masson's trichrome and picrosirius red staining 
      revealed minimal to mild collagen deposition in periportal, subcapsular, and/or 
      perisinusoidal areas in the livers of old Pygl (-/-) mice (>40 weeks). 
      Consistently, immunohistochemical analysis showed the number of cells positive 
      for alpha smooth muscle actin (alpha-SMA), a marker of activated hepatic stellate 
      cells, was increased in the livers of old Pygl (-/-) mice compared with those of 
      age-matched wild-type (WT) mice. Furthermore, old Pygl (-/-) mice had 
      inflammatory infiltrates associated with hepatic vessels in their livers along 
      with up-regulated hepatic messenger RNA levels of C-C chemokine ligand 5 
      (Ccl5/Rantes) and monocyte chemoattractant protein 1 (Mcp-1), indicating 
      inflammation, while age-matched WT mice did not. Serum levels of aspartate 
      aminotransferase and alanine aminotransferase were elevated in old Pygl (-/-) 
      mice, indicating liver damage. Conclusion: Pygl deficiency results in progressive 
      accumulation of hepatic glycogen with age and liver damage, inflammation, and 
      collagen deposition, which can increase the risk of liver fibrosis. Collectively, 
      the Pygl-deficient mouse recapitulates clinical features in patients with GSD-VI 
      and provides a model to elucidate the mechanisms underlying hepatic complications 
      associated with defective glycogen metabolism.
CI  - (c) 2019 The Authors. Hepatology Communications published by Wiley Periodicals, 
      Inc., on behalf of the American Association for the Study of Liver Diseases.
FAU - Wilson, Lane H
AU  - Wilson LH
AD  - Glycogen Storage Disease Program Department of Pediatrics University of 
      Connecticut School of Medicine Farmington CT.
FAU - Cho, Jun-Ho
AU  - Cho JH
AD  - Glycogen Storage Disease Program Department of Pediatrics University of 
      Connecticut School of Medicine Farmington CT.
FAU - Estrella, Ana
AU  - Estrella A
AD  - Glycogen Storage Disease Program Department of Pediatrics University of 
      Connecticut School of Medicine Farmington CT.
FAU - Smyth, Joan A
AU  - Smyth JA
AD  - Connecticut Veterinary Medical Diagnostic Laboratory Department of Pathobiology 
      and Veterinary Science University of Connecticut Storrs CT.
FAU - Wu, Rong
AU  - Wu R
AD  - Biostatistics Center Connecticut Convergence Institute for Translation in 
      Regenerative Engineering University of Connecticut Health Center Farmington CT.
FAU - Chengsupanimit, Tayoot
AU  - Chengsupanimit T
AD  - Glycogen Storage Disease Program University of Florida College of Medicine 
      Gainesville FL.
FAU - Brown, Laurie M
AU  - Brown LM
AD  - Glycogen Storage Disease Program University of Florida College of Medicine 
      Gainesville FL.
FAU - Weinstein, David A
AU  - Weinstein DA
AD  - Glycogen Storage Disease Program Department of Pediatrics University of 
      Connecticut School of Medicine Farmington CT.
AD  - Glycogen Storage Disease Program Connecticut Children's Medical Center Hartford 
      CT.
FAU - Lee, Young Mok
AU  - Lee YM
AUID- ORCID: 0000-0002-6304-8883
AD  - Glycogen Storage Disease Program Department of Pediatrics University of 
      Connecticut School of Medicine Farmington CT.
LA  - eng
PT  - Journal Article
DEP - 20190924
PL  - United States
TA  - Hepatol Commun
JT  - Hepatology communications
JID - 101695860
PMC - PMC6824077
EDAT- 2019/11/09 06:00
MHDA- 2019/11/09 06:01
PMCR- 2019/09/24
CRDT- 2019/11/09 06:00
PHST- 2019/03/13 00:00 [received]
PHST- 2019/08/27 00:00 [accepted]
PHST- 2019/11/09 06:00 [entrez]
PHST- 2019/11/09 06:00 [pubmed]
PHST- 2019/11/09 06:01 [medline]
PHST- 2019/09/24 00:00 [pmc-release]
AID - HEP41426 [pii]
AID - 10.1002/hep4.1426 [doi]
PST - epublish
SO  - Hepatol Commun. 2019 Sep 24;3(11):1544-1555. doi: 10.1002/hep4.1426. eCollection 
      2019 Nov.