Nerve growth factor receptor TrkA signaling in streptozotocin-induced type 1 diabetes rat brain

Vines, Katie; Li, Rongzi; Geetha, Thangiah; Carroll, Chad C.; Babu, Jeganathan Ramesh

doi:10.1016/j.bbrc.2019.04.162

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…Akt1 is also activated by hypoxia-inducible factors which are required for proper tissue reaction in hypoxia-induced PrU also (Jing et al 2015 ). The AKT-pathway is also involved in both NGF and VEGF signaling (Huang et al 2015 ; Jere et al 2019 ), and TrkA decline in db/db mice may drive AKT-pathway impairment (Vines et al 2019 ). It is interesting to note that Mmp13, the only downregulated gene in db/db, appears to exert its pro-healing action through Akt signaling (Toriseva et al 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…AKT-pathway dysfunction in diabetic mice, which has been indicated as a possible cause of wound healing impairment (Huang et al 2015 ), is somewhat complex, involving AKT isoform switches, phosphorylation, and de-phosphorylation in the different phases of wound healing (coagulation, inflammation, proliferation, and remodeling) (Maurer et al 2014 ; Vines et al 2019 ; Jere et al 2019 ; Khorami et al 2020 ). A transient pharmacological activation of the PI3K-Akt-mTOR signaling axis has been considered a novel clinical intervention strategy to accelerate wound (ulcer) healing (Squarize et al 2010 ), and we recently demonstrated that the pro-healing effect of a mutated form of rhNGF includes Akt regulation (Giuliani et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds

et al. 2022

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Experimental models for chronic skin lesions are excision and pressure ulcer, defined as “open” and “closed” lesions, respectively, only the latter characterized by tissue hypoxia. Moreover, systemic diseases, such as diabetes mellitus, affect wound repair. Thus, models for testing new therapies should be carefully selected according to the expected targets. In this study, we present an extensive and comparative histological, immunohistochemical, and molecular characterization of these two lesions in diabetic (db/db) and non-diabetic (C57BL/6 J) mice. In db/db mice, we found significant reduction in PGP9.5-IR innervation, reduction of capillary network, and reduced expression of NGF receptors. We found an increase in VEGF receptor Kdr expression, and the PI3K-Akt signaling pathway at the core of the altered molecular network. Db/db mice with pressure ulcers showed an impairment in the molecular regulation of hypoxia-related genes (Hif1a, Flt1, and Kdr), while extracellular matrix encoding genes (Itgb3, Timp1, Fn1, Col4a1) were upregulated by hyperglycemia and lesions. Overall, the molecular analysis suggests that db/db mice have a longer inflammatory phase of the wound repair process, delaying the progression toward the proliferation and remodeling phases.

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