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.

Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds / Baldassarro, Vito Antonio; Lorenzini, Luca; Giuliani, Alessandro; Cescatti, Maura; Alastra, Giuseppe; Pannella, Micaela; Imbimbo, Bruno Pietro; Villetti, Gino; Calzà, Laura; Giardino, Luciana. - In: CELL & TISSUE RESEARCH. - ISSN 1432-0878. - ELETTRONICO. - 388:3(2022), pp. 595-613. [10.1007/s00441-022-03624-x]

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

Baldassarro, Vito Antonio;Lorenzini, Luca;Cescatti, Maura;Alastra, Giuseppe;Pannella, Micaela;Calzà, Laura;Giardino, Luciana
2022

Abstract

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.
2022
Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds / Baldassarro, Vito Antonio; Lorenzini, Luca; Giuliani, Alessandro; Cescatti, Maura; Alastra, Giuseppe; Pannella, Micaela; Imbimbo, Bruno Pietro; Villetti, Gino; Calzà, Laura; Giardino, Luciana. - In: CELL & TISSUE RESEARCH. - ISSN 1432-0878. - ELETTRONICO. - 388:3(2022), pp. 595-613. [10.1007/s00441-022-03624-x]
Baldassarro, Vito Antonio; Lorenzini, Luca; Giuliani, Alessandro; Cescatti, Maura; Alastra, Giuseppe; Pannella, Micaela; Imbimbo, Bruno Pietro; Villetti, Gino; Calzà, Laura; Giardino, Luciana
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/903923
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