RESUMO
Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3'UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.
Assuntos
Injúria Renal Aguda/genética , Apoptose/genética , Células Epiteliais/patologia , Túbulos Renais/patologia , RNA Longo não Codificante/genética , Sepse/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/genética , Injúria Renal Aguda/complicações , Animais , Ceco/patologia , Regulação para Baixo/genética , Proteína Semelhante a ELAV 1/metabolismo , Perfilação da Expressão Gênica , Ligadura , Lipopolissacarídeos , Modelos Biológicos , Punções , Estabilidade de RNA/genética , RNA Longo não Codificante/metabolismo , Ratos Sprague-Dawley , Sepse/complicações , Proteína Supressora de Tumor p53/genéticaRESUMO
Macrophages are a group of immune cells with pluripotency and plasticity that can differentiate into different phenotypes under different microenvironments in vitro and in vivo. In the development of pulmonary fibrosis, there are alveolar macrophages and interstitial macrophages, which are polarized to different cell phenotypes at different stages of development. And their polarized phenotypes include M1 macrophages and M2 macrophages. In the inflammation early stages of pulmonary fibrosis, the increase of classical activated macrophages are helpful to clear pathogenic microorganisms and promote the progress of inflammation. In the fibrosis stage, the alternatively activated macrophages increased, which inhibiting the inflammatory reaction or directly promoting tissue fibrosis, on the other hand, it also promoting the fibrosis degradation. To clarify the polarization and polarization mechanisms of macrophages in pulmonary fibrosis will be conducive to the treatment of pulmonary fibrosis. In IPF, the polarization mechanism of M1 and M2 is closely related to TGF-β1/Smad. TGF-β1/Smad pathway plays an important regulatory role in liver fibrosis, renal fibrosis, myocardial fibrosis, scars, tumors and other diseases. Blocking the signaling of TGF-β1 by Smad3 and Smad4 is beneficial to inhibit the polarization of AM, which in turn helps to inhibit the progression of IPF.
Assuntos
Humanos , Fibrose , Inflamação , Macrófagos , Fibrose Pulmonar , Transdução de SinaisRESUMO
To study the evolution of Chinese ancient and modern pharmacopoeia standards and compare the domestic and foreign pharmacopoeias, further understand the international requirements on chrysanthemum quality, and establish a more suitable and modern standard system for high quality Chrysanthemi Flos pieces. Newly Revised Materia Medica, Welfare Pharmacy, Collected Essentials of Species of Materia Medica (Bencao Pinhui Jingyao), Chinese Pharmacopoeia and other herbal remedies in various generations were reviewed to summarize the evolution of domestic standards on Chrysanthemi Flos pieces. Then they were compared with those in European Pharmacopoeia, United States Pharmacopoeia, Japanese Pharmacopoeia and other foreign Pharmacopoeias to establish a modern and international high-quality Chrysanthemi Flos pieces standard system with Chinese medicine characteristics and produce more internationally recognized high-quality Chinese medicine pieces.
