All Trans Retinoic Acid (ATRA) progresses alveolar epithelium regeneration by involving diverse signalling pathways in emphysematous rat - 28/10/20
, Amit Kumar Tyagi b , Jai Prakash Muyal a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Highlights |
• | ATRA therapy leads to alveolar regeneration. |
• | Proliferation/differentiation/EMT leads to alveolar regeneration. |
• | ATRA attenuates the deregulated pathways (Notch, Hedgehog, Wnt, TGFβ and BMP). |
• | ATRA leads to alveolar regeneration via amelioration of deregulated pathways. |
Abstract |
Introduction |
Pulmonary emphysema is characterized by destruction of alveoli leading to inadequate oxygenation, disability and frequently death. This destruction was understood so far as irreversible. Published data has shown that ATRA (All Trans Retinoic Acid) reverses elastase-induced emphysema in rats. However, the molecular mechanisms governing regeneration process are so far unknown.
Objective |
To examine the therapeutic potential of ATRA on various molecular pathways and their coordination towards governance of alveolar epithelial regeneration in emphysematous rats.
Methods |
Emphysema was induced by elastase versus saline in Sprague-Dawley rats. On days 26–37, rats received daily intraperitoneal injections with ATRA (500 μg/kg b.w.) versus olive-oil. Lungs were removed at day 38 for histopathology and investigation of relative mRNA and protein expressions.
Results |
Histopathological analysis has shown that losses of alveoli were recovered in therapy (EA) group. Moreover, expressions of markers genes for alveolar cell proliferation, differentiation and EMT events at mRNA and protein levels were significantly increased in EA group than emphysema group (ES). Upon validation at genomics level, expressions of components of Notch, Hedgehog, Wnt, BMP and TGFβ pathways were significantly attenuated in EA group when compared with ES and were well comparable with the healthy group.
Conclusion |
Therapeutic supplementation of ATRA rectifies the deregulated Notch, Hedgehog, Wnt, BMP and TGFβ pathways in emphysema condition, resulting in alveolar epithelium regeneration. Hence, ATRA may prove to be a potential drug in the treatment of emphysema. Nevertheless, elaborated studies are to be conducted.
Le texte complet de cet article est disponible en PDF.Keywords : Alveolar regeneration, Emphysema, All Trans Retinoic Acid
Plan
Vol 131
Article 110725- novembre 2020 Retour au numéro
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