Resistin

Proinflammatory bioactive molecule (hormone) secreted by the subcutaneous white adipose tissue (WAT). Resistin belongs to the group of adipokines.

Resistin and psoriasis:

In rodents, resistin is mainly produced by the WAT, whereas in humans it is mainly secreted by immune and epithelial cells. Although the WAT is not the primary source of resistin in humans, its production in the WAT increases in obesity (Johnston A et al. 2008; Su X et al. 2020). Elevated levels of resistin have been found in patients with psoriasis and are positively related to the severity of the disease (Žužul K et al. 2022). The role of resistin in psoriasis begins with its binding to Toll-like receptors (TLR) 4 and cysteine-rich ankle-like protein 1 receptors, which activates important signaling pathways such as nuclear factor κB (NF-κB) .

This activation induces the production of proinflammatory cytokines such as TNF-α, IL-6 and IL-1β, which play a central role in the inflammatory cascade observed in psoriasis (Taouis M et al. 2021). As a result, the recruitment of immune cells into the skin is promoted, which exacerbates inflammation.

In addition, resistin directly influences keratinocyte behavior, which is crucial for the development of psoriatic lesions. It activates the NF-κB and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways, leading to the upregulation of genes related to cell cycle and cell survival, such as human telomerase reverse transcriptase and caveolin-1 (Mahmoud MA et al. 2006). This process leads to increased keratinocyte proliferation and impaired differentiation, which contributes to the formation and persistence of psoriatic lesions. In addition, resistin affects cellular apoptosis and disrupts the balance necessary to maintain skin homeostasis. By inhibiting apoptosis pathways such as PI3K/AKT and MAPK/Extracellular Signal-Regulated Kinase, resistin leads to increased keratinocyte survival and impaired renewal, which further exacerbates plaque formation.

Finally, resistin promotes angiogenesis in psoriatic lesions by activating signaling pathways that enhance endothelial cell proliferation and modulate the expression of angiogenesis-related genes and chemokines, including vascular endothelial growth factor(VEGF) receptor (VEGFR) 1, VEGFR2, VEGFA, and matrix metalloproteinases.

In summary, resistin plays a critical mediating role in WAT and psoriatic lesions by promoting inflammatory responses, enhancing immune cell activity, influencing keratinocyte proliferation and maturation, and promoting angiogenesis. Overall, these effects exacerbate the pathological course of psoriasis. Future studies could investigate the potential of metabolic interventions such as weight reduction or insulin sensitization treatments to jointly regulate resistin levels and psoriasis pathology.

1. Johnston A et al. (2008) Obesity in psoriasis: Leptin and resistin as mediators of cutaneous inflammation. Br J Dermatol 159:342-350.
2. Mahmoud MA et al. (2006) Expression of telomerase reverse transcriptase in psoriatic lesional skin. Dis Markers 22:265-269.
3. Su X et al. (2020) The important role of leptin in modulating the risk of dermatological diseases. Front Immunol11:5935642020.
4. Taouis M et al. (2021) Is resistin the master link between inflammation and inflammation-related chronic diseases? Mol Cell Endocrinol 533:1113412021.
5. Žužul K et al. (2022) The association between the severity of psoriasis and obesity based on the analysis of visceral fat index and serum levels of tumor necrosis factor-α, interleukin-6, and resistin. Acta Dermatovenerol Croat 30: 8-17.