| Full text | |
| Author(s): |
Pinto, Bruna Fernandes
;
Lopes, Priscila Hess
;
Trufen, Carlos Eduardo Madureira
;
Ching, Ana Tung Ching
;
de Azevedo, Inacio de Loyola M. Junqueira
;
Nishiyama-Jr, Milton Yutaka
;
de Souza, Marcelo Medina
;
Pohl, Paula C.
;
Tambourgi, Denise V.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 26, n. 7, p. 20-pg., 2025-03-26. |
| Abstract | |
Dermonecrosis resulting from Loxosceles spider envenomation, primarily driven by the enzyme sphingomyelinase D (SMase D), is characterized by severe inflammation and nonhealing wounds. SMases can be classified as Class I or II based on their structural characteristics. Class I exhibits greater dermonecrotic activity than Class II; however, the intracellular mechanisms responsible for this difference remain poorly understood. The differential transcriptomics analysis of human keratinocytes treated with each toxin revealed that Class I primarily activates pathways associated with proteolytic activity and apoptosis. In contrast, Class II uniquely upregulates key genes, including PIM-1, MCL-1, PAI-1, p21, and c-FOS, which support cell survival and inhibit apoptosis. These pathways also facilitate tissue repair and keratinocyte proliferation during wound healing, particularly through signaling mechanisms involving Substance P and VEGF-A. RT-qPCR confirmed these findings, with protein level evaluations indicating the sustained upregulation of VEGF-A exclusively in keratinocytes treated with Class II. We identified Substance P and VEGF-A as potential therapeutic targets for managing cutaneous loxoscelism, providing valuable insights into the cellular mechanisms underlying the distinct toxic effects of the two SMase D isoforms. By elucidating these pathways, this study enhances our understanding of loxoscelism's pathophysiology and highlights strategies for therapeutic intervention in dermonecrotic injuries caused by spider venom. (AU) | |
| FAPESP's process: | 20/03718-3 - Understanding the local reactions induced by Loxosceles venoms and their main toxins |
| Grantee: | Bruna Fernandes Pinto |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |