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11/10/2022

Vall d'Hebron identifies a new therapeutic target for cutaneous lupus erythematosus

Investigadores de Reumatologia, Dermatologia i Anatomia Patològica
Dra. Cristina Solé i Dra. Teresa Moliné
Investigadores al grup de Reumatologia del VHIR

11/10/2022

Lesions present low levels of miR-885-5p, and this increases keratinocyte proliferation, the attraction of inflammatory cells and also the production of inflammatory mediators.

Cutaneous Lupus Erythematosus (CLE) is an autoimmune disease characterized by the presence of rashes, sores and atrophy of the skin, especially in sunlight. Unlike systemic lupus erythematosus (SLE), in which there are manifestations in different organs, the lesions that appear in CLE appear only on the skin. Currently, the biological mechanisms by which CLE occurs are not well understood. With the aim of deepening the knowledge of this disease, a study led by the Rheumatology research group of Vall d'Hebron Research Institute (VHIR) (Dr. Josefina Cortés-Hernández and Dr. Cristina Solé), in collaboration with the Dermatology (Dr. Gloria Aparicio) and Anatomic Pathology (Dr. Berta Ferrer and Teresa Moliné) Services of Vall d'Hebron University Hospital, has identified a new therapeutic target. The work has been published in Journal of Investigative Dermatology, one of the most prestigious journals in dermatology.

The work builds on previous studies showing that miR-885-5p microRNA levels are reduced in skin lesions in CLE. MicroRNAs are small molecules that are responsible for regulating multiple genes. Although miR-885-5p is known to play an important role in skin development and physiology and wound healing, its role in the appearance of lesions is unknown. "Now we wanted to verify the abnormal expression of miR-885-5p in CLE and decipher the molecular mechanisms that are related to the development of the disease", says Dr. Cristina Solé, researcher at the Lupus Unit, in the Rheumatology group at VHIR.

To do so, researchers studied cells obtained from biopsies of 20 CLE patients and 20 healthy people. "We have observed that keratinocytes (the main cells of the skin) from CLE patients have lower levels of miR-885-5p, and this increases their proliferation, the attraction of lymphocyte cells and also the production of inflammatory mediators", explains Dr. Josefina Cortés, head of the Lupus Unit, in the Rheumatology group at VHIR. The levels of miR-885-5p decrease, for example, with ultraviolet B (UVB) light and with the presence of inflammatory cytokines, such as type I interferons.

The authors also investigated the molecular mechanisms involved in the lesions. In this regard, they determined that the decrease in miR-885-5p levels leads to skin inflammation through the NF-κB factor. In addition, it increases PSMB5 factor, which is related to increased keratinocyte proliferation. On the other hand, inhibition of miR-885-5p increases the ability of skin cells to attract inflammatory cells through TRAF1.

"Data suggest that miR-885-5p would be a potential therapeutic target for the treatment of cutaneous lupus erythematosus, as it would decrease the inflammation that characterizes the lesions", the researchers conclude. The same microRNA, however, can regulate several genes at the same time, so in future studies it will be necessary to identify the best form of administration to increase the specificity of the treatment and to find the best efficacy and minimize side effects.

miR-885-5p would be a potential therapeutic target for the treatment of cutaneous lupus erythematosus, as it would decrease the inflammation that characterizes the lesions.

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