TY - JOUR
T1 - Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue
AU - Massey, Susan Christine
AU - Hawkins-Daarud, Andrea
AU - Gallaher, Jill
AU - Anderson, Alexander R.A.
AU - Canoll, Peter
AU - Swanson, Kristin R.
N1 - Funding Information:
This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-0781824, the James S. McDonnell Foundation Collaborative Activity Award #220020264, the National Institutes of Health (U01CA220378, U54CA210180, U54CA143970, U54CA193489, R01NS060752, R01CA16437, P01CA42045), the Ben and Catherine Ivy Foundation, the University of Washington Academic Pathology Fund, the James D. Murray Endowed Chair in the Nancy and Buster Alvord Brain Tumor Center at the University of Washington. The content is solely the responsibility of the authors. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation or any other supporting agencies. As always, KRS is eternally grateful to the unwavering support of Dr. E. C. “Buster” Alvord, Jr. (1923–2010); may this manuscript continue to honor his memory and foster his scientific legacy.
Publisher Copyright:
© 2019, Society for Mathematical Biology.
PY - 2019/6/15
Y1 - 2019/6/15
N2 - Paracrine PDGF signaling is involved in many processes in the body, both normal and pathological, including embryonic development, angiogenesis, and wound healing as well as liver fibrosis, atherosclerosis, and cancers. We explored this seemingly dual (normal and pathological) role of PDGF mathematically by modeling the release of PDGF in brain tissue and then varying the dynamics of this release. Resulting simulations show that by varying the dynamics of a PDGF source, our model predicts three possible outcomes for PDGF-driven cellular recruitment and lesion growth: (1) localized, short duration of growth, (2) localized, chronic growth, and (3) widespread chronic growth. Further, our model predicts that the type of response is much more sensitive to the duration of PDGF exposure than the maximum level of that exposure. This suggests that extended duration of paracrine PDGF signal during otherwise normal processes could potentially lead to lesions having a phenotype consistent with pathologic conditions.
AB - Paracrine PDGF signaling is involved in many processes in the body, both normal and pathological, including embryonic development, angiogenesis, and wound healing as well as liver fibrosis, atherosclerosis, and cancers. We explored this seemingly dual (normal and pathological) role of PDGF mathematically by modeling the release of PDGF in brain tissue and then varying the dynamics of this release. Resulting simulations show that by varying the dynamics of a PDGF source, our model predicts three possible outcomes for PDGF-driven cellular recruitment and lesion growth: (1) localized, short duration of growth, (2) localized, chronic growth, and (3) widespread chronic growth. Further, our model predicts that the type of response is much more sensitive to the duration of PDGF exposure than the maximum level of that exposure. This suggests that extended duration of paracrine PDGF signal during otherwise normal processes could potentially lead to lesions having a phenotype consistent with pathologic conditions.
KW - Gliosis
KW - Oligodendroglial progenitors
KW - Platelet-derived growth factor
KW - Scarring
UR - http://www.scopus.com/inward/record.url?scp=85062045542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062045542&partnerID=8YFLogxK
U2 - 10.1007/s11538-019-00587-z
DO - 10.1007/s11538-019-00587-z
M3 - Article
C2 - 30796683
AN - SCOPUS:85062045542
SN - 0092-8240
VL - 81
SP - 1645
EP - 1664
JO - The Bulletin of Mathematical Biophysics
JF - The Bulletin of Mathematical Biophysics
IS - 6
ER -