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Il est souvent nécessaire de faire les premières études sur un modèle simplifié, mais nous avons vu dans le chapitre 1, l’important effet des composants dermiques sur la réparation des dommages induits par les rayons UV dans l’épiderme. Il serait donc pertinent de compléter l’étude de l’impact d’un régime d’irradiation chronique sur l’épiderme en utilisant des modèles de peaux reconstruites.

Les travaux antérieurs du laboratoire ont démontré que les fibroblastes répondaient différemment à une CLUV que les kératinocytes pour ce qui est de la réparation des CPD

(Berube et al., 2018, Drigeard Desgarnier et al., 2017, Drigeard Desgarnier and Rochette, 2018). La présence d’un derme sous-jacent et les changements induits dans celui-ci pourraient modifier la communication dermo-épidermique et donc la réponse de l’épiderme à l’irradiation chronique. D’autant plus que des études ont mis en évidence que des changements induits dans les fibroblastes par une exposition aux rayons UV ou par le vieillissement impactent les kératinocytes. L'exposition solaire répétée de fibroblastes dermiques induit des changements dans l'expression génique, dans la traduction de protéines et une diminution de la capacité de prolifération en culture (Drigeard Desgarnier et al., 2017, Gilchrest, 1980). Des théories récentes suggèrent aussi que le dérèglement des processus de réponse post-irradiation des kératinocytes pourrait être lié à la diminution de la fonctionnalité des fibroblastes retrouvés dans les peaux âgées et endommagées (Lewis et al., 2010). De plus, l'accumulation de cellules dermiques sénescentes au cours du vieillissement, serait associée à une expression altérée des protéases et des cytokines et créerait un microenvironnement tissulaire plus favorable à la croissance tumorale des cellules épithéliales (DePinho, 2000, Krtolica et al., 2001). Les effets d’une exposition chronique aux rayons UV sur les fibroblastes pourraient ainsi contribuer à modifier la communication dermo-épidermique et donc impacter la réparation des CPD et la mort cellulaire UV-induite au niveau épidermique.

Finalement, il serait intéressant d’observer les dommages induits par une lumière représentant plus fidèlement l’exposition réelle de l’homme. Ainsi, l’utilisation d’une lumière solaire simulée permettrait de conclure quant aux dommages induits par l’action concertée des rayons UVA et UVB, et ce, dans leurs proportions physiologiques.

Conclusion

Les travaux réalisés dans cette thèse permettent de mieux comprendre les réponses des kératinocytes épidermiques aux rayonnements UV. Ils mettent en lumière l’importance de la nature des modèles utilisés et montrent qu’en complexifiant ces modèles pour les rendre plus physiologiques, nous pourrions caractériser plus justement les réponses de la peau au stress UV. Une meilleure compréhension de cette réponse pourrait permettre le développement de nouveaux outils permettant d’accélérer la réparation des CPD et donc de limiter l’initiation des cancers les plus répandus que sont les cancers cutanés.

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