Regulation of wound healing and fibrosis by galectins

Abstract

Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues and organs and participate in different physiological and pathological molecular reactions in vivo. Wound healing is the basic process of traumatic disease recovery. Wound healing involves three overlapping stages: inflammation, proliferation, and remodelling. Furthermore, a comparison of wound healing with the tumour microenvironment revealed that galectin plays a key role in the wound healing process. The current review describes the role of galectin in inflammation, angiogenesis, re-epithelialisation, and fibrous scar formation and evaluates its potential as a therapeutic drug for wounds.

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https://doi.org/10.1007/s00109-022-02207-1
REVIEW
Regulation ofwound healing andfibrosis bygalectins
DongYu1,2· MingBu1,2· PingYu1· YapingLi1,2· YangChong1,2
Received: 2 December 2021 / Revised: 29 April 2022 / Accepted: 10 May 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022
Abstract
Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues
and organs and participate in different physiological and pathological molecular reactions invivo. Wound healing is the basic
process of traumatic disease recovery. Wound healing involves three overlapping stages: inflammation, proliferation, and
remodelling. Furthermore, a comparison of wound healing with the tumour microenvironment revealed that galectin plays
a key role in the wound healing process. The current review describes the role of galectin in inflammation, angiogenesis,
re-epithelialisation, and fibrous scar formation and evaluates its potential as a therapeutic drug for wounds.
Keywords Galectin· Wound healing· Inflammation· Angiogenesis· Re-epithelialisation· Fibrosis
Introduction
Galectins are a family of proteins that binds to β-galactose
glucoside, all of which have one or two highly conserved
carbohydrate-recognition domains (CRDs) [1]. In total, 15
types of galectins have been discovered in mammals, of
which 11 exist in humans. They can be divided into three
groups according to their structures: (I) prototype galectin:
galectin-1 (Gal-1), -2, -5, -7, -10, -11, -13, -14, and -15,
which contain a dimerised CRD; (II) complex galectin: Gal-
4, -6, -8, -9, and -12, which contain two CRDs connected
by short peptides; and (III) chimeric galectin: Gal-3, with a
C-terminal CRD and an N-terminal tail [1, 2]. Galectins are
present in the cytoplasm and nucleus; they can be secreted
out of cells through various mechanisms [3]. Galectins can
bind to bacteria and agglutinate, and some galectins (Gal-4
and -8) can kill bacteria directly without activating other
factors such as complement factors [4, 5].
Galectins were first studied in-depth in tumour-related
fields. Galectins are key participants in mediating the inter-
action between tumour cells and host endothelial cells,
immune cells, and extracellular matrix (ECM), and they
participate in the regulation of tumour development and
progression, such as fibroblast activation, angiogenesis,
and immune response [6, 7]. Galectin has a high affinity
for glycans containing galactose glucoside on cell surfaces
and ECM glycoproteins [8, 9], which indicates its potential
involvement in wound healing. Some advances have been
made in studying the role of galectins in wound healing,
such as inflammation regulation, macrophage polarisation,
angiogenesis, fibroblast to myofibroblast transformation,
and re-epithelialisation [1, 10–12]. The regulatory role
of galectins in tumour and wound healing makes them an
active candidate for treating cancer and skin wounds. The
present article reviews the role of galectins in various stages
of wound healing and discusses their potential and develop-
ment prospects in skin wound treatment (Table1).
Role ofgalectin inskin wound inflammation
Most galectins participate in the inflammation process in
the body. Gal-1 has an anti-inflammatory effect, and its
messenger RNA (mRNA) is up-regulated in the placenta
of women with preeclampsia, which is considered a foetal
response to maternal systemic infection [15]. Therapeutic
administration of Gal-1 can treat chronic T cell-dependent
inflammation, such as hepatitis, arthritis, and colitis [53–55].
A subcutaneous injection of Gal-1 can accelerate the heal-
ing of pathological wounds in diabetic mice [20]. In addi-
tion, Gal-1 can stimulate mitogen-activated protein kinase
* Yang Chong
092016@yzu.edu.cn
1 Department ofTraditional Chinese Medicine, The Affiliated
Hospital ofYangzhou University, Yangzhou University,
Yangzhou225000, Jiangsu, China
2 Department ofMedical College, Yangzhou University,
Yangzhou225000, Jiangsu, China
/ Published online: 19 May 2022
Journal of Molecular Medicine (2022) 100:861–874
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