Melanopsin as the UVA photoreceptor and its relationship with pigmentation, DNA repair, biological clock and components of the HPA axis: a novel pharmacological target?

• Grant number: 18/14728-0
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2019 - March 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Maria de Lauro Castrucci
• Grantee: Ana Maria de Lauro Castrucci
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Leonardo Vinícius Monteiro de Assis ; Maria Nathália de Carvalho Magalhães Moraes Figueira Borges

Abstract

The mammalian photosensitive system committed to non-image forming processes has been well characterized in the eyes. The components of this system are the opsins, biological sensors of light. Opsins are also present in the skin cells, but the biological processes they regulate are largely unknown. Recent evidence resulting from our work and others indicate the role of these sensors in the regulation of pigmentation by light and ultraviolet radiation and in keratinocyte differentiation. Skin cells also possess a complex system of temporal control, which is capable of "marking time" thus providing the cutaneous cells with time information. This system is composed of clock genes, which time key processes such as proliferation, DNA repair, among others. Our group is a world leader in both research fields. In addition, the skin is by itself a complex neuroendocrine system able to synthesize and secrete a variety of chemical messengers identical to the ones produced by the central neuroendocrine axis. It has been demonstrated that UVB and UVA radiation directly stimulate the skin to synthesize several messengers which exert local as well as systemic actions. Till now, the mechanism of UVA has been poorly investigated and the receptor mediating these effects is still unknown. We have demonstrated that melanopsin is a UVA sensor, therefore we hypothesize that UVA excites skin melanopsin, which triggers a signaling cascade culminating with pigmentation processes, DNA repair, modulation of the biological clock and local and central synthesis of hormones. To answer these questions, we will expose wild type and melanopsin knockout mice to UVA and assess pigmentation, DNA repair, gene and protein quantification of clock genes, hormone quantification and total sequencing of mRNA. Through the use of animal models and advanced techniques of molecular biology we will establish the role of melanopsin in the skin, opening the perspective of a novel pharmacological target. (AU)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE ASSIS, LEONARDO VINICIUS MONTEIRO; CASTRUCCI, ANA MARIA DE LAURO. Comments regarding Hiramoto et al.. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, v. 20, n. 10, p. 2-pg., 2021-09-01. (18/14728-0, 17/24615-5)

DE ASSIS, LEONARDO VINICIUS MONTEIRO; TONOLLI, PAULO NEWTON; MORAES, MARIA NATHALIA; BAPTISTA, MAURICIO S.; CASTRUCCI, ANA MARIA DE LAURO. ow does the skin sense sun light? An integrative view of light sensing molecule. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY C-PHOTOCHEMISTRY REVIEWS, v. 47, JUN 2021. (17/24615-5, 18/14728-0, 13/07937-8)

MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO VINICIUS MONTEIRO; PROVENCIO, IGNACIO; CASTRUCCI, ANA MARIA DE LAURO. Opsins outside the eye and the skin: a more complex scenario than originally thought for a classical light sensor. Cell and Tissue Research, v. 385, n. 3, JUL 2021. (17/26651-9, 17/24615-5, 18/14728-0)

SUA-CESPEDES, CRISTHIAN D.; DAVID, DANIELA DANTAS; SOUTO-NETO, JOSE A.; LIMA, OTONIEL GONCALVES; MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO V. MONTEIRO; CASTRUCCI, ANA MARIA DE LAURO. Low Temperature Effect on the Endocrine and Circadian Systems of Adult Danio rerio. FRONTIERS IN PHYSIOLOGY, v. 12, NOV 24 2021. (18/23043-0, 18/16511-8, 17/26651-9, 18/14728-0, 17/24615-5, 18/23915-8)

ORTIZ-ROMERO, P. L.. The time for new biomarkers in mycosis fungoides/Sezary syndrome is here. British Journal of Dermatology, v. 185, n. 2, p. 3-pg., 2021-06-06. (18/14728-0, 17/24615-5)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; MENDES, DAVI; SILVA, MATHEUS MOLINA; KINKER, GABRIELA SARTI; PEREIRA-LIMA, ISABELLA; MORAES, MARIA NATHALIA; MARTINS MENCK, CARLOS FREDERICO; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin mediates UVA-dependent modulation of proliferation, pigmentation, apoptosis, and molecular clock in normal and malignant melanocytes. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1867, n. 10, OCT 2020. (14/27287-0, 19/19435-3, 13/24337-4, 17/24615-5, 12/50214-4, 18/16511-8, 17/26651-9, 17/18781-0, 18/14728-0, 17/24217-0)

FORNI, MARIA FERNANDA; ALBERTO DOMINGUEZ-AMOROCH, OMAR; MONTEIRO DE ASSIS, LEONARDO VINICIUS; KINKER, GABRIELA SARTI; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA; SARAIVA CAMARA, NIELS OLSEN. An Immunometabolic Shift Modulates Cytotoxic Lymphocyte Activation During Melanoma Progression in TRPA1 Channel Null Mice. FRONTIERS IN ONCOLOGY, v. 11, MAY 10 2021. (18/16511-8, 18/14728-0, 17/16711-4, 17/26651-9, 17/24615-5)

REZENDE PAULA, ANA BEATRIZ; MIRANDA, DENISE DE COUTINHO; NOGUEIRA, FRANCIANE TOLEDO; DE LAURO CASTRUCCI, ANA MARIA; ISOLDI, MAURO CESAR. Does a high-fat diet affect the circadian clock, or is it the other way around? A systematic review. Nutrition Research, v. 84, p. 1-13, DEC 2020. (18/14728-0)

DE ASSIS, LEONARDO VINICIUS MONTEIRO; MORAES, MARIA NATHALIA; MENDES, DAVI; SILVA, MATHEUS MOLINA; MENCK, CARLOS FREDERICO MARTINS; CASTRUCCI, ANA MARIA DE LAURO. Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes. CURRENT ISSUES IN MOLECULAR BIOLOGY, v. 43, n. 3, p. 1436-1450, DEC 2021. (18/16511-8, 17/24615-5, 17/26651-9, 17/18781-0, 19/19435-3, 18/14728-0, 17/24217-0)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; LACERDA, JOSE THALLES; MORAES, MARIA NATHALIA; DOMINGUEZ-AMOROCHO, OMAR ALBERTO; KINKER, GABRIELA SARTI; MENDES, DAVI; SILVA, MATHEUS MOLINA; MARTINS MENCK, CARLOS FREDERICO; SARAIVA CAMARA, NIELS OLSEN; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin (Opn4) is an oncogene in cutaneous melanoma. COMMUNICATIONS BIOLOGY, v. 5, n. 1, p. 15-pg., 2022-05-13. (19/19435-3, 19/25129-2, 17/24217-0, 17/26651-9, 18/16511-8, 12/50214-4, 18/14728-0, 17/24615-5, 17/18781-0, 20/04524-8, 13/24337-4, 17/16711-4)

PORTES, ALEXANDRE MARTINS OLIVEIRA; PAULA, ANA BEATRIZ REZENDE; DE MIRANDA, DENISE COUTINHO; RESENDE, LETICIA TERESINHA; COELHO, BIANCA IARA CAMPOS; TELES, MARIA CECILIA; JARDIM, ISABELA ALCANTARA BARRETTO ARAUJO; NATALI, ANTONIO JOSE; CASTRUCCI, ANA MARIA DE LAURO; ISOLDI, MAURO CESAR. A systematic review of the effects of cold exposure on pathological cardiac remodeling in mice. Journal of Thermal Biology, v. 114, p. 11-pg., 2023-06-13. (18/14728-0, 17/24615-5)

DE ASSIS, L. V. M.; CASTRUCCI, A. M. L.. Novel light-dependent and light-independent functions of opsin 5. British Journal of Dermatology, v. 185, n. 2, p. 3-pg., 2021-04-07. (18/14728-0, 17/24615-5)

LACERDA, JOSE THALLES; GOMES, PATRICIA R. L.; ZANETTI, GIOVANNA; MEZZALIRA, NATHANA; LIMA, OTONIEL G.; DE ASSIS, LEONARDO V. M.; GULER, ALI; CASTRUCCI, ANA MARIA; MORAES, MARIA NATHALIA. Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 13, p. 24-pg., 2022-07-01. (17/24615-5, 21/01659-2, 14/16412-9, 20/04524-8, 18/23915-8, 18/16511-8, 13/02131-5, 12/50214-4, 18/14728-0, 17/26651-9, 21/09923-0)

SUA-CESPEDES, CRISTHIAN; LACERDA, JOSE THALLES; ZANETTI, GIOVANNA; DAVID, DANIELA DANTAS; MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO V. M.; CASTRUCCI, ANA MARIA L.. Melanopsin (OPN4) is a novel player in skin homeostasis and attenuates UVA-induced effects. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 242, p. 15-pg., 2023-04-03. (16/00696-3, 13/07937-8, 19/19005-9, 21/01659-2, 17/26651-9, 18/23043-0, 18/16511-8, 12/50214-4, 12/12663-1, 18/14728-0, 17/24615-5, 20/04524-8, 14/16412-9)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA. The molecular clock in the skin, its functionality, and how it is disrupted in cutaneous melanoma: a new pharmacological target?. CELLULAR AND MOLECULAR LIFE SCIENCES, v. 76, n. 19, p. 3801-3826, OCT 2019. (12/50214-4, 18/14728-0)

GALVAO VALDIVIA, LUIS FELIPE; CASTRO, ERIQUE; DOS SANTOS EICHLER, ROSANGELA APARECIDA; MORENO, MAYARA FRANZOI; DE SOUSA, ERICA; RODRIGUES JARDIM, GIOVANNA FREITAS; PEIXOTO, ALBERT SOUZA; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA; NEDERGAARD, JAN; et al. Cold acclimation and pioglitazone combined increase thermogenic capacity of brown and white adipose tissues but this does not translate into higher energy expenditure in mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 324, n. 4, p. 16-pg., 2023-04-01. (17/26651-9, 21/02953-1, 19/01763-4, 20/04159-8, 18/14728-0, 21/03717-0, 17/24615-5, 19/25943-1)