Psoriasis Study Finds Key Anti-Angiogenic Protein Depleted in Lesional Skin

Psoriasis affects millions of people worldwide, yet the molecular signals that drive its scaly, inflamed plaques remain only partially understood. A new study from researchers at Sohag University and Qena University in Egypt has turned the spotlight on one such signal: pigment epithelium-derived factor, or PEDF, a protein best known for its ability to block the growth of new blood vessels. Published in the Archives of Dermatological Research, the cross-sectional investigation measured PEDF both in the bloodstream and directly within the skin of patients with psoriasis vulgaris, and its findings add a surprising twist to what scientists thought they knew about this molecule’s role in the disease.

PEDF is a 50-kilodalton glycoprotein that was first identified in the conditioned media of cultured human retinal pigment epithelial cells in the early 1990s, where it displayed potent neuronal differentiative activity. Subsequent work revealed that it belongs to the serpin family of proteins, although it lacks the protease-inhibiting function that characterizes most serpins. Instead, PEDF has earned a reputation as one of the most powerful endogenous inhibitors of angiogenesis known to biology, exceeding even the effects of thrombospondin-1 in some assay systems. Beyond its vascular effects, PEDF participates in metabolism, acting as an adipokine released from adipose tissue and influencing insulin sensitivity, which is one reason researchers suspected it might connect psoriasis with the metabolic syndrome.

The rationale for the Egyptian study rested on two converging lines of evidence. First, psoriasis is fundamentally a disease of disordered angiogenesis: the dermal papillae of psoriatic plaques are packed with dilated, tortuous capillaries, and vascular endothelial growth factor and other pro-angiogenic mediators are abundantly expressed in lesional skin. Second, earlier reports had suggested that circulating PEDF concentrations were elevated in psoriasis patients, raising the possibility that the protein could serve as a biomarker linking the skin disease to cardiovascular and metabolic comorbidity. However, few studies had simultaneously examined serum levels and tissue expression, and none had rigorously tested whether PEDF tracks with clinical severity or metabolic status in the same cohort.

To address these gaps, the team, led by dermatologist Amr Abdelhamed, enrolled 26 patients with psoriasis vulgaris and 26 age- and sex-matched healthy controls. Each patient underwent a detailed clinical assessment, including calculation of the Psoriasis Area and Severity Index, the standard composite measure that grades erythema, induration, and desquamation across body regions. The investigators also screened participants for metabolic syndrome using established diagnostic criteria encompassing waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Blood samples were drawn for serum PEDF quantification by enzyme-linked immunosorbent assay, while punch biopsies were taken from both lesional plaque skin and peri-lesional, normally appearing skin for immunohistochemical staining of PEDF expression.

The serum results defied expectations. Median serum PEDF concentration in the psoriasis group was 21.5 nanograms per milliliter, with a range spanning 13 to 162, compared with 22.2 nanograms per milliliter, ranging from 7 to 193, in the controls. The difference was statistically non-significant, with a p-value of 0.261, meaning that circulating PEDF offered no meaningful discrimination between patients and healthy individuals in this cohort. This finding stands in tension with earlier studies that reported elevated serum PEDF in psoriasis, and it underscores how cohort characteristics, assay methodology, and sample size can shape biomarker conclusions in dermatology research.

The tissue data told a far more striking story. Immunohistochemical analysis revealed a median PEDF expression score of 1.4, on a scale ranging from 0.5 to 2.2, in lesional psoriatic skin. That figure was dramatically lower than the median of 5, ranging from 2 to 5.5, observed in the peri-lesional skin of the same patients, and lower still than the median of 5.8, ranging from 5.7 to 7.3, in the skin of healthy controls. Both comparisons yielded p-values below 0.001, indicating differences that are extremely unlikely to have arisen by chance. In other words, the very skin that bears the hallmark of psoriasis is markedly depleted of one of the body’s chief anti-angiogenic defenses, while the skin immediately adjacent to the plaques retains near-normal expression.

This spatial gradient carries important mechanistic implications. Angiogenesis in psoriasis is thought to be fueled by an imbalance between pro-angiogenic drivers, such as vascular endothelial growth factor, interleukin-8, and angiopoietins released by keratinocytes and inflammatory cells, and anti-angiogenic brakes like PEDF and thrombospondin-1. The new data suggest that the loss of the PEDF brake is a local phenomenon confined to diseased tissue rather than a systemic shift detectable in the blood. That localization is consistent with the histopathology of psoriatic plaques, where elongated and dilated capillaries in the papillary dermis supply nutrients to the hyperproliferative epidermis above. It also aligns with experimental work showing that topical application of PEDF-derived anti-angiogenic peptides can ameliorate psoriasis-like skin changes in animal models.

Perhaps the most clinically consequential negative finding concerned the metabolic syndrome. Psoriasis patients are known to carry an elevated burden of obesity, dyslipidemia, hypertension, and insulin resistance, and PEDF has been implicated in insulin resistance in obesity, with adipose-derived PEDF rising as fat mass expands. Yet in this study, neither serum nor tissue PEDF levels correlated with the presence or absence of metabolic syndrome, nor with the PASI score, with all corresponding p-values exceeding 0.05. The authors also explored univariate correlations between PEDF levels and various histopathological features, reported in supplementary tables, without uncovering significant associations. The disconnect suggests that PEDF is unlikely to serve as a convenient blood-based biomarker tying psoriasis severity to cardiometabolic risk, at least in populations resembling this one.

Several caveats temper the conclusions. The sample size of 26 patients per group was modest, calculated with power analysis software but still vulnerable to type II error, particularly for correlation analyses that require larger cohorts to detect weak associations. The cross-sectional design captures a single time point, so it cannot establish whether reduced tissue PEDF is a cause or a consequence of plaque formation. Serum PEDF concentrations also varied enormously within both groups, spanning nearly an order of magnitude, which may reflect confounders such as body composition, age, and comorbid disease that a larger study could adjust for more thoroughly. Longitudinal follow-up of patients during effective therapy would help determine whether PEDF expression rebounds as plaques resolve.

Even so, the study sharpens the picture of psoriasis as a disease in which the local vascular microenvironment is decisively tilted toward vessel growth. The near absence of PEDF in lesional skin, contrasted with its preservation in neighboring tissue, provides a measurable target for therapeutic intervention and reinforces the rationale for anti-angiogenic strategies in dermatology. It also serves as a cautionary tale about biomarker research: a molecule can be abundant in the circulation yet irrelevant to the diseased tissue, and only paired serum-and-tissue studies can reveal that distinction. As researchers continue to map the angiogenic circuitry of psoriasis, PEDF now stands as a locally silenced guardian whose restoration might one day complement existing anti-inflammatory treatments.

Subject of Research: Serum and tissue levels of the anti-angiogenic protein PEDF in patients with psoriasis vulgaris

Article Title: Evaluation of serum and tissue levels of pigment epithelium-derived factor (PEDF) in patients with psoriasis vulgaris

Article References: Evaluation of serum and tissue levels of pigment epithelium-derived factor (PEDF) in patients with psoriasis vulgaris. (n.d.). https://doi.org/10.1007/s00403-026-04887-y

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04887-y

Keywords: psoriasis vulgaris, PEDF, angiogenesis, metabolic syndrome, PASI score, serum biomarkers, immunohistochemistry, lesional skin, dermatology research, Archives of Dermatological Research, Evaluation, serum