It is well known that miRNAs modulate the expression of several targets at once and in this way they activate or inhibit pathways [33], [34].
Among these, tyrosine kinases of the Src family require ROS for a full enzymatic activity; in turn, Src can regulate ROS production in localized subcellular districts, including mitochondria, where Src kinases can locate to modulate the activity of several targets.
Also, the molecular targets that modulate several key pathological factors of acne can be aimed to optimize the therapeutic outcome.
In the kidney, HNF-1β, a transcriptional factor, has been shown to modulate activities of several target genes in tubular epithelia, namely Umod, Pkhd1, Pkd2 and Tg737/Polaris.
In addition, PfMyb1 was capable to modulate expression of several targeted genes [ 5, 15].
In particular, the α and γ isoforms of the p38 MAPK [ 47, 48] appear to modulate several proinflammatory pathways in RASFs and have therefore already been targeted in clinical trials.
For example, PA has been shown to modulate several proteins, including phosphatidylinositol-4-phosphate-5-kinase, protein phosphatase 1, and mammalian target of rapamycin.
FOXO transcription proteins modulate several cellular functions including proliferation, apoptosis, stress resistance, inflammation migration, and metabolism through regulation of multiple transcriptional targets.
Curcumin mediates its effects by modulating several important molecular targets, including transcription factors NF- κB, Ap1 and specificity protein 1 (Sp1).
We speculate that the reason why 126/KD may expand HSC without exhaustion might be because, rather than affecting a single regulator, miR-126 likely modulates several functionally important targets in interconnected pathways that together orchestrate an HSC program.
