Document Detail

High and low molecular weight hyaluronic acid differentially regulate human fibrocyte differentiation.
MedLine Citation:
PMID:  22022512     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da).
METHODS AND FINDINGS: In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation.
CONCLUSIONS: We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13.
Anu S Maharjan; Darrell Pilling; Richard H Gomer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-11
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-24     Completed Date:  2012-02-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e26078     Citation Subset:  IM    
Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, Texas, United States of America.
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MeSH Terms
Antibodies / pharmacology
Antigens, CD44 / immunology,  metabolism
Cell Differentiation / drug effects*
Cell Separation
Cell Survival / drug effects
Cells, Cultured
Endocytosis / drug effects
Fibroblasts / cytology*,  drug effects*,  metabolism
Hyaluronic Acid / chemistry*,  pharmacology*
Hyaluronoglucosaminidase / pharmacology
Interleukin-13 / pharmacology
Interleukin-4 / pharmacology
Leukocytes, Mononuclear / cytology,  drug effects
Molecular Weight
Monocytes / cytology,  drug effects
Serum Amyloid P-Component / pharmacology
Grant Support
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD44; 0/Interleukin-13; 0/Serum Amyloid P-Component; 207137-56-2/Interleukin-4; 9004-61-9/Hyaluronic Acid; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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