A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation

Abstract

Melanogenesis is the process of melanin synthesis through keratinocytes-melanocytes interaction, which is triggered by the damaging effect of ultraviolet-B (UVB) rays. It is known that melanogenesis influences diverse cellular responses, including cell survival and apoptosis, via complex mechanisms of feedback and crosstalk. Therefore, an attempt to suppress melanin production by modulating the melanogenesis pathway may induce perturbations in the apoptotic balance of the cells in response to UVB irradiation, which results in various skin diseases such as melasma, vitiligo, and skin cancer. To identify such appropriate target strategies for the reduction of UVB-induced melanin synthesis, we reconstructed the melanogenesis signaling network and developed a Boolean network model. Mathematical simulations of the melanogenesis network model revealed that the inhibition of beta-catenin in the melanocytes effectively reduce melanin production while having minimal influence on the apoptotic balance of the cells. Exposing cells to a beta-catenin inhibitor decreased pigmentation but did not significantly change the B-cell Chronic lymphocytic leukemia/lymphoma 2 expression, a potent regulator of apoptotic balance. Thus, our systems analysis suggests that the inhibition of beta-catenin may be the most appropriate target strategy for the reduction of UVB-induced skin pigmentation.

Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway

“…UVB is radiation at 280–320 nm, in the natural ultraviolet band of the spectrum and is associated with skin conditions such as sunburn and photocarcinogenesis 48 67 68 . Many studies have reported that various natural agents (e.g., epigallocatechin gallate 69 , pomegranate polyphenol extract 70 , and resveratrol 36 ) have photoprotective effects against UV injury.…”

Attractor landscape analysis of colorectal tumorigenesis and its reversion

“…To investigate the biological properties of the human signaling network, we analyzed the input–output relationship of the network [ 19 , 21 ]. In the Boolean simulation, the states of all nodes in the network were updated according to their assigned logical rules at each simulation step.…”

“…To investigate the transition in the cellular state of the human signaling network during colorectal tumorigenesis, we performed the attractor landscape analysis of the human signaling network [ 10 , 21 , 22 ]. The attractor landscape is composed of attractors and their basins of attraction where an attractor is one of the steady-states of the network and the basin of an attractor represents a set of network states that converge to the attractor.…”

Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients

“…Furthermore, it was found that β-catenin functionally interacts with the MITF protein itself and inhibition of β-catenin can effectively reduce the melanin production. 27 Relatively small sample size was the main limitation of the current work. Therefore, we recommend further large-scaled studies to validate our findings as this is the first study that evaluates…”