Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution

Yimu Yang, Sarah M. Haeger, Matthew A. Suflita, Fuming Zhang, Kyrie L. Dailey, James F. Colbert, Joshay A. Ford, Mario A. Picon, Robert Stearman, Lei Lin, Xinyue Liu, Xiaorui Han, Robert J. Linhardt, Eric P. Schmidt

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The endothelial glycocalyx is a heparan sulfate (HS)-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenousmechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-Type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncturemediated) endothelial glycocalyx degradation.Weusedmass spectrometry, surface plasmon resonance, and in vitro studies of human andmouse samples to determine the structure ofHS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulatingHS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1-mediated glycocalyx reconstitution.

Original languageEnglish (US)
Pages (from-to)727-737
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume56
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Glycocalyx
Fibroblast Growth Factors
Degradation
Lung
Heparitin Sulfate
Sepsis
heparitinsulfate lyase
Receptor, Fibroblast Growth Factor, Type 1
Surface plasmon resonance
Spectrometry
Repair
Tissue
Surface Plasmon Resonance
Vascular System Injuries
Recovery
Transgenic Mice
Enzymes
Ligation
Edema
Spectrum Analysis

Keywords

  • Fibroblast growth factor
  • Heparan sulfate
  • Sepsis

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Yang, Y., Haeger, S. M., Suflita, M. A., Zhang, F., Dailey, K. L., Colbert, J. F., ... Schmidt, E. P. (2017). Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. American Journal of Respiratory Cell and Molecular Biology, 56(6), 727-737. https://doi.org/10.1165/rcmb.2016-0338OC

Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. / Yang, Yimu; Haeger, Sarah M.; Suflita, Matthew A.; Zhang, Fuming; Dailey, Kyrie L.; Colbert, James F.; Ford, Joshay A.; Picon, Mario A.; Stearman, Robert; Lin, Lei; Liu, Xinyue; Han, Xiaorui; Linhardt, Robert J.; Schmidt, Eric P.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 56, No. 6, 01.06.2017, p. 727-737.

Research output: Contribution to journalArticle

Yang, Y, Haeger, SM, Suflita, MA, Zhang, F, Dailey, KL, Colbert, JF, Ford, JA, Picon, MA, Stearman, R, Lin, L, Liu, X, Han, X, Linhardt, RJ & Schmidt, EP 2017, 'Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution', American Journal of Respiratory Cell and Molecular Biology, vol. 56, no. 6, pp. 727-737. https://doi.org/10.1165/rcmb.2016-0338OC
Yang, Yimu ; Haeger, Sarah M. ; Suflita, Matthew A. ; Zhang, Fuming ; Dailey, Kyrie L. ; Colbert, James F. ; Ford, Joshay A. ; Picon, Mario A. ; Stearman, Robert ; Lin, Lei ; Liu, Xinyue ; Han, Xiaorui ; Linhardt, Robert J. ; Schmidt, Eric P. / Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. In: American Journal of Respiratory Cell and Molecular Biology. 2017 ; Vol. 56, No. 6. pp. 727-737.
@article{64de0e9e21224ff1bf15850e96544ceb,
title = "Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution",
abstract = "The endothelial glycocalyx is a heparan sulfate (HS)-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenousmechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-Type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncturemediated) endothelial glycocalyx degradation.Weusedmass spectrometry, surface plasmon resonance, and in vitro studies of human andmouse samples to determine the structure ofHS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulatingHS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1-mediated glycocalyx reconstitution.",
keywords = "Fibroblast growth factor, Heparan sulfate, Sepsis",
author = "Yimu Yang and Haeger, {Sarah M.} and Suflita, {Matthew A.} and Fuming Zhang and Dailey, {Kyrie L.} and Colbert, {James F.} and Ford, {Joshay A.} and Picon, {Mario A.} and Robert Stearman and Lei Lin and Xinyue Liu and Xiaorui Han and Linhardt, {Robert J.} and Schmidt, {Eric P.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1165/rcmb.2016-0338OC",
language = "English (US)",
volume = "56",
pages = "727--737",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution

AU - Yang, Yimu

AU - Haeger, Sarah M.

AU - Suflita, Matthew A.

AU - Zhang, Fuming

AU - Dailey, Kyrie L.

AU - Colbert, James F.

AU - Ford, Joshay A.

AU - Picon, Mario A.

AU - Stearman, Robert

AU - Lin, Lei

AU - Liu, Xinyue

AU - Han, Xiaorui

AU - Linhardt, Robert J.

AU - Schmidt, Eric P.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - The endothelial glycocalyx is a heparan sulfate (HS)-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenousmechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-Type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncturemediated) endothelial glycocalyx degradation.Weusedmass spectrometry, surface plasmon resonance, and in vitro studies of human andmouse samples to determine the structure ofHS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulatingHS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1-mediated glycocalyx reconstitution.

AB - The endothelial glycocalyx is a heparan sulfate (HS)-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenousmechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-Type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncturemediated) endothelial glycocalyx degradation.Weusedmass spectrometry, surface plasmon resonance, and in vitro studies of human andmouse samples to determine the structure ofHS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulatingHS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1-mediated glycocalyx reconstitution.

KW - Fibroblast growth factor

KW - Heparan sulfate

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=85020181211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020181211&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2016-0338OC

DO - 10.1165/rcmb.2016-0338OC

M3 - Article

C2 - 28187268

AN - SCOPUS:85020181211

VL - 56

SP - 727

EP - 737

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 6

ER -