Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.10.3.1 (
tyrosinase
)
9,065
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and signaling via VEGFRs extends beyond the classical roles in blood vessel formation. We previously showed VEGFRs were also expressed in epidermal keratinocytes and activation of VEGFR-2 by ultraviolet B (UVB) was involved in the pro-survival mechanism. Here, we show that both VEGF165 and UVB enhanced the expression of VEGFRs (including
VEGFR-1
, VEGFR-2 and NRP-1) in normal human melanocytes, and increased expression of VEGFRs by UVB was mediated through hypoxia and oxidative stress. Also, VEGF165 and UVB promoted tyrosine phosphorylation of
VEGFR-1
and VEGFR-2, and UVB-induced phosphorylation of
VEGFR-1
and VEGFR-2 required PKA but not P38 MAPK. In addition, UVB and VEGF165 contributed to the over-expression of melanogenic proteins in melanocytes, which could be reduced by neutralization of
VEGFR-1
and/or VEGFR-2. UVB, but not VEGF165 promoted cell proliferation, while neutralization of
VEGFR-1
and/or VEGFR-2 abolished this effect. UVB showed stronger than VEGF165 in promoting
tyrosinase
activity and melanin production, while neutralization of VEGFR-2 was stronger in reducing these effects than that of
VEGFR-1
. Furthermore, tranexamic acid (TA) decreased
tyrosinase
activity and melanin production via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that VEGFRs are functionally involved in UVB-induced melanogenesis, and TA can inhibit melanogenesis at least in part by targeting VEGFRs in melanocytes.
...
PMID:Activation of VEGF receptors in response to UVB promotes cell proliferation and melanogenesis of normal human melanocytes. 3187 75
Melasma is a common but complex skin condition concerning cosmetic problems. Tranexamic acid (TA) has been proved to be effective in treatment of melasma with still unclear mechanisms. Here, we show that VEGF165 enhanced the expression of VEGF receptors (VEGFRs, including
VEGFR-1
, VEGFR-2 and NRP-1) in human umbilical vein endothelial cells (HUVECs), which was attenuated by TA. VEGF165 also promoted tyrosine phosphorylation of
VEGFR-1
and VEGFR-2 in HUVECs, which was again abolished by TA. TA further showed similar effects to neutralization of
VEGFR-1
and VEGFR-2 in inhibiting cell proliferation, migration, invasion and tube formation of HUVECs induced by VEGF165, suggesting that TA could inhibit angiogenesis by targeting VEGFRs in HUVECs. In addition, VEGF165 enhanced the expression of VEGFRs and promoted tyrosine phosphorylation of
VEGFR-1
and VEGFR-2 in normal human melanocytes, which were also attenuated by TA. Furthermore, TA showed similar effects to neutralization of
VEGFR-1
and VEGFR-2 in inhibiting
tyrosinase
activity, melanin production and even melanogenic proteins induced by VEGF165, suggesting that TA could reduce melanogenesis via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that TA can inhibit angiogenesis and melanogenesis
in vitro
at least in part by targeting VEGFRs, which may offer a new understanding of the pathogenesis of melasma as well as the molecular mechanism for TA in treatment of the disease.
...
PMID:Tranexamic Acid Inhibits Angiogenesis and Melanogenesis
in Vitro
by Targeting VEGF Receptors. 3230 43
