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Role for heat shock protein 90α in the proliferation and migration of HaCaT cells and in the deep second-degree burn wound healing in mice.

Zhang Y, Bai X, Wang Y, Li N, Li X, Han F, Su L, Hu D - PLoS ONE (2014)

Bottom Line: The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90α)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop.Experiments performed with a human keratinocyte cell line--HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing.In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.

View Article: PubMed Central - PubMed

Affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, China.

ABSTRACT
Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90α)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90α at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line--HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing. Consistently, topical application of Hsp90α in the early stage of deep second-degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.

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An in vivo study showing the effects of Hsp90α on burn wound healing.(A) Deep second-degree burn wounds (20 mm in diameter) on Balb/c mice were treated topically with saline or Hsp90α (1 µg/ml) daily for 5 days following burn injury. In 17-DMAG group, 17-DMAG at 25 mg/kg b.w. was injected intraperitoneally three times per week for two weeks prior to burn treatment, and then saline was applied topically. (B) Histogram quantified the wound size on day 0, 5, 9, 13 and 21 (n = 5 in each group). (C) Hsp90α promoted the re-epithelialization of deep second-degree burn wound. On day 7 after burn injury, biopsies of burned and unburned skins were excised from control, Hsp90α, and 17-DMAG-treated groups. Samples were then HE stained and photographed with an FSX100 microscope. Images were reconstituted to show the whole healed and unhealed areas. Area between two vertical red lines indicated unhealed skin, while area with black dotted lines indicated newly formed epidermis. Green arrows marked the advancing migrating epithelial tongues on each side of the wounds.
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pone-0103723-g006: An in vivo study showing the effects of Hsp90α on burn wound healing.(A) Deep second-degree burn wounds (20 mm in diameter) on Balb/c mice were treated topically with saline or Hsp90α (1 µg/ml) daily for 5 days following burn injury. In 17-DMAG group, 17-DMAG at 25 mg/kg b.w. was injected intraperitoneally three times per week for two weeks prior to burn treatment, and then saline was applied topically. (B) Histogram quantified the wound size on day 0, 5, 9, 13 and 21 (n = 5 in each group). (C) Hsp90α promoted the re-epithelialization of deep second-degree burn wound. On day 7 after burn injury, biopsies of burned and unburned skins were excised from control, Hsp90α, and 17-DMAG-treated groups. Samples were then HE stained and photographed with an FSX100 microscope. Images were reconstituted to show the whole healed and unhealed areas. Area between two vertical red lines indicated unhealed skin, while area with black dotted lines indicated newly formed epidermis. Green arrows marked the advancing migrating epithelial tongues on each side of the wounds.

Mentions: To examine the therapeutic potential of Hsp90α on burn wound healing, microscopic and histological experiments were performed. Highly purified human recombinant Hsp90α protein was dissolved at 1 µg/ml in saline, and locally applied to burn wounds daily for the first 5 days following burn injury. As shown in Fig. 6A, the wound size in control group was slowly reduced each day. In Hsp90α-treated group, the process of wound healing was more rapid, with gradually smaller wound each day (p<0.05). While mice pre-treated with 17-DMAG showed an slower response on wound healing even than the control. The degree of edema and hyperemia in Hsp90α group was also less pronounced than that in other two groups. Wound size was measured on day 0, 5, 9, 13 and 21 (Fig. 6B, p<0.05). Results suggested that Hsp90α could significantly accelerate wound closure and shorten the time course of healing.


Role for heat shock protein 90α in the proliferation and migration of HaCaT cells and in the deep second-degree burn wound healing in mice.

Zhang Y, Bai X, Wang Y, Li N, Li X, Han F, Su L, Hu D - PLoS ONE (2014)

An in vivo study showing the effects of Hsp90α on burn wound healing.(A) Deep second-degree burn wounds (20 mm in diameter) on Balb/c mice were treated topically with saline or Hsp90α (1 µg/ml) daily for 5 days following burn injury. In 17-DMAG group, 17-DMAG at 25 mg/kg b.w. was injected intraperitoneally three times per week for two weeks prior to burn treatment, and then saline was applied topically. (B) Histogram quantified the wound size on day 0, 5, 9, 13 and 21 (n = 5 in each group). (C) Hsp90α promoted the re-epithelialization of deep second-degree burn wound. On day 7 after burn injury, biopsies of burned and unburned skins were excised from control, Hsp90α, and 17-DMAG-treated groups. Samples were then HE stained and photographed with an FSX100 microscope. Images were reconstituted to show the whole healed and unhealed areas. Area between two vertical red lines indicated unhealed skin, while area with black dotted lines indicated newly formed epidermis. Green arrows marked the advancing migrating epithelial tongues on each side of the wounds.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128658&req=5

pone-0103723-g006: An in vivo study showing the effects of Hsp90α on burn wound healing.(A) Deep second-degree burn wounds (20 mm in diameter) on Balb/c mice were treated topically with saline or Hsp90α (1 µg/ml) daily for 5 days following burn injury. In 17-DMAG group, 17-DMAG at 25 mg/kg b.w. was injected intraperitoneally three times per week for two weeks prior to burn treatment, and then saline was applied topically. (B) Histogram quantified the wound size on day 0, 5, 9, 13 and 21 (n = 5 in each group). (C) Hsp90α promoted the re-epithelialization of deep second-degree burn wound. On day 7 after burn injury, biopsies of burned and unburned skins were excised from control, Hsp90α, and 17-DMAG-treated groups. Samples were then HE stained and photographed with an FSX100 microscope. Images were reconstituted to show the whole healed and unhealed areas. Area between two vertical red lines indicated unhealed skin, while area with black dotted lines indicated newly formed epidermis. Green arrows marked the advancing migrating epithelial tongues on each side of the wounds.
Mentions: To examine the therapeutic potential of Hsp90α on burn wound healing, microscopic and histological experiments were performed. Highly purified human recombinant Hsp90α protein was dissolved at 1 µg/ml in saline, and locally applied to burn wounds daily for the first 5 days following burn injury. As shown in Fig. 6A, the wound size in control group was slowly reduced each day. In Hsp90α-treated group, the process of wound healing was more rapid, with gradually smaller wound each day (p<0.05). While mice pre-treated with 17-DMAG showed an slower response on wound healing even than the control. The degree of edema and hyperemia in Hsp90α group was also less pronounced than that in other two groups. Wound size was measured on day 0, 5, 9, 13 and 21 (Fig. 6B, p<0.05). Results suggested that Hsp90α could significantly accelerate wound closure and shorten the time course of healing.

Bottom Line: The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90α)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop.Experiments performed with a human keratinocyte cell line--HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing.In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.

View Article: PubMed Central - PubMed

Affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, China.

ABSTRACT
Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90α)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90α at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line--HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing. Consistently, topical application of Hsp90α in the early stage of deep second-degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.

Show MeSH
Related in: MedlinePlus