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AuthorAkhtar, Saghir
AuthorChandrasekhar, Bindu
AuthorYousif, Mariam Hm
AuthorRenno, Waleed
AuthorBenter, Ibrahim F
AuthorEl-Hashim, Ahmed Z
Available date2019-04-14T04:59:58Z
Publication Date2019-03-01
Publication NameNanomedicine: Nanotechnology, Biology and Medicineen_US
Identifierhttp://dx.doi.org/10.1016/j.nano.2019.02.012
CitationAkhtar S, Chandrasekhar B, Yousif MH, Renno W, Benter IF, El-Hashim AZ. Chronic administration of nano-sized PAMAM dendrimers in vivo inhibits EGFR-ERK1/2-ROCK signaling pathway and attenuates diabetes-induced vascular remodeling and dysfunction. Nanomedicine. 2019 Mar 4;18:78-89. doi: 10.1016/j.nano.2019.02.012.
ISSN1549-9634
URIhttp://hdl.handle.net/10576/11477
AbstractWe investigated whether chronic administration of nano-sized polyamidoamine (PAMAM) dendrimers can have beneficial effects on diabetes-induced vascular dysfunction by inhibiting the epidermal growth factor receptor (EGFR)-ERK1/2-Rho kinase (ROCK)-a pathway known to be critical in the development of diabetic vascular complications. Daily administration of naked PAMAMs for up to 4 weeks to streptozotocin-induced diabetic male Wistar rats inhibited EGFR-ERK1/2-ROCK signaling and improved diabetes-induced vascular remodeling and dysfunction in a dose, generation (G6 > G5) and surface chemistry-dependent manner (cationic > anionic > neutral). PAMAMs, AG1478 (a selective EGFR inhibitor), or anti-EGFR siRNA also inhibited vascular EGFR-ERK1/2-ROCK signaling in vitro. These data showed that naked PAMAM dendrimers have the propensity to modulate key (e.g. EGFR) cell signaling cascades with associated pharmacological consequences in vivo that are dependent on their physicochemical properties. Thus, PAMAMs, alone or in combination with vasculoprotective agents, may have a beneficial role in the potential treatment of diabetes-induced vascular complications.
SponsorThis research is funded by a grant from the Research Sector at Kuwait University (MR01/13). We also acknowledge support from the OMICS Research Unit/RCF and the General Facility Grant (SRUL02/13).
Languageen
PublisherElsevier
SubjectCell signaling
SubjectDiabetes
SubjectEGFR
SubjectPolyamidoamine
SubjectVascular complications
TitleChronic administration of nano-sized PAMAM dendrimers in vivo inhibits EGFR-ERK1/2-ROCK signaling pathway and attenuates diabetes-induced vascular remodeling and dysfunction.
TypeArticle
Pagination78-89
Volume Number18


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