Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a novel modulator of TGFβ signaling. This study shows LRG1 expression is increased during wound healing. Lrg1-/- mice show delayed wound healing, altered immune cell infiltration, re-epithelialization, angiogenesis and fibroblast activation in vivo. C...

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Main Author: Liu, Chenghao
Other Authors: Wang Xiaomeng
Format: Theses and Dissertations
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/90069
http://hdl.handle.net/10220/49449
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-900692020-07-02T06:22:26Z Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing Liu, Chenghao Wang Xiaomeng School of Chemical and Biomedical Engineering Engineering::Bioengineering Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a novel modulator of TGFβ signaling. This study shows LRG1 expression is increased during wound healing. Lrg1-/- mice show delayed wound healing, altered immune cell infiltration, re-epithelialization, angiogenesis and fibroblast activation in vivo. Cell-based studies reveal that LRG1 differentially regulates TGFβ signaling pathway in keratinocytes, endothelial cells and fibroblasts. Surprisingly, LRG1 expression is significantly increased in ulcers and serum of diabetic foot ulcer patients and wounds from streptozotocin-induced diabetic mice. Under diabetic conditions, deletion of Lrg1 accelerates wound healing in mice. Western blot analysis shows reduced formation of neutrophil extracellular traps in the wounds of diabetic Lrg1-/- mice. Neutrophils isolated from Lrg1-/- mice are less susceptible to inducer of ΝΕΤs formation. Consistently, recombinant LRG1 can induce NETosis in human neutrophils by activating extracellular signal-regulated kinases. Taken together, this study provides new insights into the complex role of LRG1 in normal and diabetic wound healing. Doctor of Philosophy 2019-07-22T01:23:54Z 2019-12-06T17:40:00Z 2019-07-22T01:23:54Z 2019-12-06T17:40:00Z 2019 Thesis Liu, C. (2019). Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/90069 http://hdl.handle.net/10220/49449 10.32657/10220/49449 en 148 p. application/pdf
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Engineering::Bioengineering
spellingShingle Engineering::Bioengineering
Liu, Chenghao
Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
description Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a novel modulator of TGFβ signaling. This study shows LRG1 expression is increased during wound healing. Lrg1-/- mice show delayed wound healing, altered immune cell infiltration, re-epithelialization, angiogenesis and fibroblast activation in vivo. Cell-based studies reveal that LRG1 differentially regulates TGFβ signaling pathway in keratinocytes, endothelial cells and fibroblasts. Surprisingly, LRG1 expression is significantly increased in ulcers and serum of diabetic foot ulcer patients and wounds from streptozotocin-induced diabetic mice. Under diabetic conditions, deletion of Lrg1 accelerates wound healing in mice. Western blot analysis shows reduced formation of neutrophil extracellular traps in the wounds of diabetic Lrg1-/- mice. Neutrophils isolated from Lrg1-/- mice are less susceptible to inducer of ΝΕΤs formation. Consistently, recombinant LRG1 can induce NETosis in human neutrophils by activating extracellular signal-regulated kinases. Taken together, this study provides new insights into the complex role of LRG1 in normal and diabetic wound healing.
author2 Wang Xiaomeng
author_facet Wang Xiaomeng
Liu, Chenghao
format Theses and Dissertations
author Liu, Chenghao
author_sort Liu, Chenghao
title Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
title_short Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
title_full Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
title_fullStr Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
title_full_unstemmed Roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
title_sort roles of leucine-rich alpha-2-glycoprotein 1 in normal and diabetic wound healing
publishDate 2019
url https://hdl.handle.net/10356/90069
http://hdl.handle.net/10220/49449
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