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Repair Effects of KGF on Ischemia-Reperfusion-Induced Flap Injury via Activating Nrf2 Signaling.
J Surg Res 2019; 244:547-557JS

Abstract

BACKGROUND

Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury.

MATERIALS AND METHODS

A CoCl2-stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2-related factor 2 (Nrf2) signaling-related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot.

RESULTS

HaCAT cells treated with 40 μM CoCl2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues.

CONCLUSIONS

KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling.

Authors+Show Affiliations

Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address: xxiaoyuan_xyxie@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31351398

Citation

Mao, Yueping, et al. "Repair Effects of KGF On Ischemia-Reperfusion-Induced Flap Injury Via Activating Nrf2 Signaling." The Journal of Surgical Research, vol. 244, 2019, pp. 547-557.
Mao Y, Chen X, Xia Y, et al. Repair Effects of KGF on Ischemia-Reperfusion-Induced Flap Injury via Activating Nrf2 Signaling. J Surg Res. 2019;244:547-557.
Mao, Y., Chen, X., Xia, Y., & Xie, X. (2019). Repair Effects of KGF on Ischemia-Reperfusion-Induced Flap Injury via Activating Nrf2 Signaling. The Journal of Surgical Research, 244, pp. 547-557. doi:10.1016/j.jss.2019.06.078.
Mao Y, et al. Repair Effects of KGF On Ischemia-Reperfusion-Induced Flap Injury Via Activating Nrf2 Signaling. J Surg Res. 2019 Jul 24;244:547-557. PubMed PMID: 31351398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repair Effects of KGF on Ischemia-Reperfusion-Induced Flap Injury via Activating Nrf2 Signaling. AU - Mao,Yueping, AU - Chen,Xiaoyan, AU - Xia,Yue, AU - Xie,Xiaoyuan, Y1 - 2019/07/24/ PY - 2018/12/21/received PY - 2019/04/09/revised PY - 2019/06/19/accepted PY - 2019/7/28/pubmed PY - 2019/7/28/medline PY - 2019/7/28/entrez KW - Flap KW - Ischemia-reperfusion KW - Nrf2 signaling KW - Repair KW - rhKGF SP - 547 EP - 557 JF - The Journal of surgical research JO - J. Surg. Res. VL - 244 N2 - BACKGROUND: Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury. MATERIALS AND METHODS: A CoCl2-stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2-related factor 2 (Nrf2) signaling-related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot. RESULTS: HaCAT cells treated with 40 μM CoCl2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues. CONCLUSIONS: KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/31351398/Repair_Effects_of_KGF_on_Ischemia-Reperfusion-Induced_Flap_Injury_via_Activating_Nrf2_Signaling L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(19)30470-6 DB - PRIME DP - Unbound Medicine ER -