A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis

Abstract Chronic wounds show necroptosis from which keratinocytes must be protected to enable appropriate wound re-epithelialization and closure. Poloxamers, a class of synthetic triblock copolymers, are known to be effective against plasma membrane damage (PMD). The purpose of this study is to eval...

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Autores principales:	Puneet Khandelwal, Amitava Das, Chandan K. Sen, Sangly P. Srinivas, Sashwati Roy, Savita Khanna
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9db291b94984d8cbe44209d7f651749
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spelling	oai:doaj.org-article:f9db291b94984d8cbe44209d7f6517492021-12-02T14:28:20ZA surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis10.1038/s41598-021-82260-x2045-2322https://doaj.org/article/f9db291b94984d8cbe44209d7f6517492021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82260-xhttps://doaj.org/toc/2045-2322Abstract Chronic wounds show necroptosis from which keratinocytes must be protected to enable appropriate wound re-epithelialization and closure. Poloxamers, a class of synthetic triblock copolymers, are known to be effective against plasma membrane damage (PMD). The purpose of this study is to evaluate the efficacy of a specific poloxamer, surfactant polymer dressing (SPD), which is currently used clinically as wound care dressing, against PMD in keratinocytes. Triton X-100 (TX100) at sub-lytic concentrations caused PMD as demonstrated by the efflux of calcein and by the influx of propidium iodide and FM1-43. TX100, an inducer of necroptosis, led to mitochondrial fragmentation, depletion of nuclear HMGB1, and activation of signaling complex associated with necroptosis (i.e., activation of RIP3 and phosphorylation of MLKL). All responses following exposure of human keratinocytes to TX100 were attenuated by pre- or co-treatment with SPD (100 mg/ml). The activation and translocation of phospho-MLKL to the plasma membrane, taken together with depletion of nuclear HMGB1, characterized the observed cell death as necroptosis. Thus, our findings show that TX100-induced plasma membrane damage and death by necroptosis were both attenuated by SPD, allowing keratinocyte survival. The significance of such protective effects of SPD on keratinocytes in wound re-epithelialization and closure warrant further studies.Puneet KhandelwalAmitava DasChandan K. SenSangly P. SrinivasSashwati RoySavita KhannaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Puneet Khandelwal Amitava Das Chandan K. Sen Sangly P. Srinivas Sashwati Roy Savita Khanna A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
description	Abstract Chronic wounds show necroptosis from which keratinocytes must be protected to enable appropriate wound re-epithelialization and closure. Poloxamers, a class of synthetic triblock copolymers, are known to be effective against plasma membrane damage (PMD). The purpose of this study is to evaluate the efficacy of a specific poloxamer, surfactant polymer dressing (SPD), which is currently used clinically as wound care dressing, against PMD in keratinocytes. Triton X-100 (TX100) at sub-lytic concentrations caused PMD as demonstrated by the efflux of calcein and by the influx of propidium iodide and FM1-43. TX100, an inducer of necroptosis, led to mitochondrial fragmentation, depletion of nuclear HMGB1, and activation of signaling complex associated with necroptosis (i.e., activation of RIP3 and phosphorylation of MLKL). All responses following exposure of human keratinocytes to TX100 were attenuated by pre- or co-treatment with SPD (100 mg/ml). The activation and translocation of phospho-MLKL to the plasma membrane, taken together with depletion of nuclear HMGB1, characterized the observed cell death as necroptosis. Thus, our findings show that TX100-induced plasma membrane damage and death by necroptosis were both attenuated by SPD, allowing keratinocyte survival. The significance of such protective effects of SPD on keratinocytes in wound re-epithelialization and closure warrant further studies.
format	article
author	Puneet Khandelwal Amitava Das Chandan K. Sen Sangly P. Srinivas Sashwati Roy Savita Khanna
author_facet	Puneet Khandelwal Amitava Das Chandan K. Sen Sangly P. Srinivas Sashwati Roy Savita Khanna
author_sort	Puneet Khandelwal
title	A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
title_short	A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
title_full	A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
title_fullStr	A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
title_full_unstemmed	A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
title_sort	surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f9db291b94984d8cbe44209d7f651749
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A surfactant polymer wound dressing protects human keratinocytes from inducible necroptosis

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