RPA facilitates rescue of keratinocytes from UVB radiation damage through insulin-like growth factor-I signalling

Andrade, Melisa J and Satyamoorthy, Kapaettu (2021) RPA facilitates rescue of keratinocytes from UVB radiation damage through insulin-like growth factor-I signalling. Journal of Cell Science, 134. pp. 1-14. ISSN 0021-9533

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Abstract

UVBR-induced photolesions in genomic DNA of keratinocytes impair cellular functions and potentially determine the cell fate post-irradiation.The ability of insulin-like growth factor-I (IGF-I) to rescue epidermal keratinocytes after photodamage via apoptosis prevention and photolesion removal was recently demonstrated using in vitro twodimensional and three-dimensional skin models. Given the limited knowledge of specific signalling cascades contributing to post-UVBR IGF-I effects,we used inhibitors to investigate the impact of blockade of various signalling mediators on IGF-I photoprotection. IGF-I treatment,in the presence of signalling inhibitors, particularly TDRL-505, which targets replication protein A (RPA), impaired activation of IGF-1R downstream signalling, diminished cyclobutane pyrimidine dimer removal, arrested growth, reduced cell survival and increased apoptosis. Further, the transient partial knockdown of RPA was found to abrogate IGF-I-mediated responses in keratinocytes, ultimately affecting photoprotection and, thereby, establishing that RPA is required for IGF-I function. Our findings thus elucidate the importance of RPA in linking the damage response activation, cell cycle regulation,repair and survival pathways, separately initiated by IGF-I upon UVBRinduced damage. This information is potentially imperative for the development of effective sunburn and photodamage repair strategies

Item Type: Article
Uncontrolled Keywords: Keratinocyte; Ultraviolet radiation; DNA damage; Insulin-like growth factor; Skin models; Photodamage repair
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 08 Sep 2021 10:33
Last Modified: 08 Sep 2021 10:33
URI: http://eprints.manipal.edu/id/eprint/157269

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