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...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2019
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/90069 http://hdl.handle.net/10220/49449 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
|---|