Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits
, Martina Morelli 1, Claudia Scarponi 1, Giovanni Luca Scaglione 1, Sabatino Pallotta 1, Daniele Avitabile 2, Cristina Albanesi 1 and Stefania Madonna 1,*Round 1
Reviewer 1 Report
Dr. Laura Mercurio and colleagues have provided high-level experimental work, which supports the role of the NAMPT-mediated NAD salvage pathway in the pathogenesis of psoriasis. The authors approached this issue in a complex way by studying the involvement of the NAD salvage pathway in the cytokine production, proliferation, and differentiation of keratinocytes, fibroblasts, and endothelial cells. First of all, the results showed that among the enzymes implicated in the kynurenine-, Preiss-Handler-, and salvage pathways, the levels of IDO-1, KYNU, and NAMPT are increased accompanied by elevated NAD+ level in the psoriatic skin lesions. Furthermore, the authors revealed that NAM acts in synergy with several cytokines, enhances proliferation, and impairs the differentiation of keratinocytes. Finally, they observed that the secreted and rh NAMPT exerts pro-inflammatory and angiogenic effects on endothelial cells. The methodology and results are of good quality, the manuscript is interesting and well written. I consider this work important because these studies identify a new therapeutic target for more effective treatment of psoriasis and provide new insights into the potential risks of dietary NAD+ supplementation.
Reviewer 2 Report
Interesting and innovative research highlighting NAMPT-mediated NAD salvage pathway as a newer and potential part in psoriasis pathogenesis. Weel designed and well written study.
