In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 310, No. 1 ( 2016-01-01), p. G1-G12
Abstract:
Podoplanin/gp38 + stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38 + cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38 + cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38 + cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38 + cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45 − CD31 − Asgpr1 − liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38 hi CD133 − , gp38 low CD133 − , and gp38 − CD133 − ). Moreover, among the CD133 + cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38 − CD133 + and CD133 + gp38 + ). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38 + CD133 + cells exhibited liver progenitor cell characteristics similar to the gp38 − CD133 + population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00344.2015
Language:
English
Publisher:
American Physiological Society
Publication Date:
2016
detail.hit.zdb_id:
1477329-6
SSG:
12
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