Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Geniposide (GP) as an agonist of glucagon-like peptide-1 receptor (GLP-1R) is an iridoid glycoside from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of vitiligo vulgaris. Interaction of c-kit receptor with its ligand-SCF potent enhances the melanocytic melanogenesis, which can be repressed by norepinephrine (NE). To discover economic and efficient drug against vitiligo vulgaris, this paper addresses the action and mechanism of GP abrogating the NE-induced hypopigmentation in melanocyte. Flow cytometry exhibited the up-regulation effect of GP on NE-suppressed production of c-kit by normal human epidermal melanocyte (HEMn) in a concentration-dependent manner, and exendin-(9-39) (selective GLP-1R antagonist) appeared to alleviate the GP-stimulated expression of c-kit. However, neither NE nor GP affected the production of SCF by normal human epidermal keratinocyte (HEKn) assessed by cellular enzyme-linked immunosorbent assay. Spectrophotometry documented that GP abrogated the repression effect of NE on tyrosinase activity and melanin production in HEMn in the presence of recombination SCF significantly. The response of melanocytic melanogenesis to GP was blocked by exendin-(9-39) or K44.2 antibody (c-kit inhibitory antibody). Data from this paper provide the evidence that GP abrogates the NE-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in which c-kit expression is augmented in HEMn.
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PMID:Evidence that geniposide abrogates norepinephrine-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in melanocyte. 1848 37

Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of generalized vitiligo. Stem cell factor from keratinocyte recognizes and activates its receptor c-kit carried by melanocyte to potent enhance melanocytic melanogenesis that can be suppressed by norepinephrine. This study addresses the action and mechanism of geniposide enhancing melanogenesis in norepinephrine-exposed normal human epidermal melanocyte. Flow cytometry results from this study exhibited the augmentation effect of geniposide on production of c-kit receptor by norepinephrine-exposed normal human epidermal melanocyte. However, geniposide did not affect the production of stem cell factor by norepinephrine-exposed normal human epidermal keratinocyte assessed by cellular enzyme-linked immunosorbent assay (ELISA). ELISA indicated that at the presence of stem cell factor, geniposide was capable of elevating the level of extracellular signal-regulated kinase 1/2 phosphorylation within norepinephrine-exposed normal human epidermal melanocyte, which is known to be involved in stem cell factor/c-kit downstream signalling. And inhibition of c-kit with inhibitory antibody K44.2 completely blocked the increase in geniposide-stimulated extracellular signal-regulated kinase 1/2 phosphorylation. In addition, spectrophotometry demonstrated the enhancement effect of geniposide on melanogenesis (tyrosinase activity and melanin production) in norepinephrine-exposed normal human epidermal melanocyte at the presence of stem cell factor, which was blocked by c-kit inhibitory antibody K44.2. Data from this study suggest that geniposide can enhance melanogenesis by stem cell factor/c-kit signalling in which the expression of c-kit receptor is augmented in norepinephrine-exposed normal human epidermal melanocyte.
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PMID:Geniposide enhances melanogenesis by stem cell factor/c-Kit signalling in norepinephrine-exposed normal human epidermal melanocyte. 1859