Sphingosine 1-phosphate protective effect on human proximal tubule cells submitted to an in vitro ischemia model: the role of JAK2/STAT3.

Autor: de Assis JL; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Grelle GMRS; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Laboratório de Metabolômica, LADETEC, Instituto de Química - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Fernandes AM; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., da Silva Aniceto B; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Pompeu P; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., de Mello FV; Serviço de Citometria do Instituto de Pediatria e Puericultura Martagão Gesteira (IPPMG) - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Garrett R; Laboratório de Metabolômica, LADETEC, Instituto de Química - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Valverde RHF; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Einicker-Lamas M; Laboratório de Biomembranas, Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. einicker@biof.ufrj.br.
Jazyk: angličtina
Zdroj: Journal of physiology and biochemistry [J Physiol Biochem] 2024 Aug 19. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1007/s13105-024-01038-7
Abstrakt: Acute kidney injury is a serious public health problem worldwide, being ischemia and reperfusion (I/R) the main lesion-aggravating factor that contributes to the evolution towards chronic kidney disease. Nonetheless, intervention approaches currently available are just considered palliative options. In order to offer an alternative treatment, it is important to understand key factors involved in the development of the disease including the rescue of the affected cells and/or the release of paracrine factors that are crucial for tissue repair. Bioactive lipids such as sphingosine 1-phosphate (S1P) have significant effects on the modulation of signaling pathways involved in tissue regeneration, such as cell survival, proliferation, differentiation, and migration. The main objective of this work was to explore the protective effect of S1P using human kidney proximal tubule cells submitted to a mimetic I/R lesion, via ATP depletion. We observed that the S1P pre-treatment increases cell survival by 50% and preserves the cell proliferation capacity of injured cells. We showed the presence of different bioactive lipids notably related to tissue repair but, more importantly, we noted that the pre-treatment with S1P attenuated the ischemia-induced effects in response to the injury, resulting in higher endogenous S1P production. All receptors but S1PR3 are present in these cells and the protective and proliferative effect of S1P/S1P receptors axis occur, at least in part, through the activation of the SAFE pathway. To our knowledge, this is the first time that S1PR4 and S1PR5 are referred in these cells and also the first indication of JAK2/STAT3 pathway involvement in S1P-mediated protection in an I/R renal model.
(© 2024. The Author(s) under exclusive licence to University of Navarra.)
Databáze: MEDLINE
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