Triptolide protects podocytes via autophagy in immunoglobulin A nephropathy

Abstract

Triptolide is often used to treat patients with immunoglobulin A nephropathy (IgAN), especially in Asia. However, its detailed mechanism remains unclear. In vitro experiments were conducted with podocytes exposed to aggregated IgA (aIgA)-MSC1097-conditioned media. A total of four groups were compared in this study: A control group (CON); a healthy supernatant group (HEAs); an IgAN supernatant group (IgANs); and a triptolide group (TRI). First, aggregated IgA1 (aIgA1) was generated by heating monomeric IgA1 (mIgA1) from IgAN patients or healthy subjects. Next, the conditioned supernatant of MSC-1097 cells cultured with aIgA1 (100 mg/l) from IgAN patients (IgANs) or healthy subjects (HEAs) or without aIgA1 (CON) were harvested and used to incubate MPC5 cells. MPC5 cells in the TRI group were cultured with triptolide (10 ng/ml) and conditioned media from MSC-1097 cells cultured with aIgA1 from IgAN patients. After 24 h of treatment, MPC5 cells were collected to measure autophagy-related protein levels, including microtubule-associated protein light chain 3 (LC3), p62, cluster of differentiation (CD)63, phosphorylated-protein kinase B (Akt), Akt, p-mammalian target of rapamycin (mTOR), and mTOR, via western blotting, immunofluorescence or both, and to determine apoptosis by flow cytometry. All the results showed no difference between the CON and the HEAs. Compared to the CON and the HEAs, MPC5 cells in the IgANs group showed reduced autophagy, which was presented as decreased levels of LC3-II and CD63, as well as accumulation of p62, and an increased podocyte apoptosis rate. This was partly rescued by the addition of triptolide. Moreover, the p-mTOR/mTOR ratio increased in the IgANs group and decreased in the TRI group. Therefore, these results suggest that triptolide protects podocyte autophagy in IgAN patients.

Morroniside Inhibits H2O2-Induced Podocyte Apoptosis by Down-Regulating NOX4 Expression Controlled by Autophagy In Vitro

“…The autophagy activity of podocytes has a bidirectional change under different injury conditions. For example, in patients with diabetes (Wu et al, 2018;Zhao et al, 2018;Li et al, 2020) and IgA nephropathy (Liang et al, 2018), decreased podocyte autophagy activity is observed; while in systemic lupus erythematosus (SLE) (Jin et al, 2018) or adriamycin-induced models of nephrotic syndrome (Yu et al, 2018), podocyte autophagy activity is found to be increased. Yu et al (2019) observed an increase in the number of autophagosomes and the expression of autophagy-related proteins such as LC3B-II and Beclin-1 in podocytes stimulated by lupus autoantibodies.…”

Leptin deficiency in mice counteracts imiquimod (IMQ)‐induced psoriasis‐like skin inflammation while leptin stimulation induces inflammation in human keratinocytes

“…A screening of 102 cytokines using a proteome array was performed to highlight new and interesting pro-inflammatory proteins upregulated in human keratinocytes upon leptin stimulation. We observed that leptin stimulated secretion of several psoriasis-related cytokines, for example CCL20, a CCR6 ligand, strongly chemotactic for lymphocytes and upregulated by IL-17A, IL-22 and TNFα 46 ; IL-6, CXCL-1 and IL-8, pro-inflammatory cytokines increased in psoriatic skin, associated with chemoattraction of lymphocytes and keratinocyte proliferation 33,39,47 ; hBD2, which is overexpressed in psoriatic skin and also induced by TNFα and IFNγ 48,49 but also IL-17A and IL-22 50 and MMP9, a collagenase acting as an angiogenesis promoting factor, which is increased in psoriasis. 51 Induced secretions of IL-6 and IL-8 by leptin have previously been reported 7,29 ; however, induced secretions of CCL20, CXCL1 and MMP9 extend the list of psoriasisrelated proteins stimulated by leptin.…”

The Active Compounds and Therapeutic Target of Tripterygium wilfordii Hook. f. in Attenuating Proteinuria in Diabetic Nephropathy: A Review

“…Conversely, the activation of mTORC1 in podocytes, which results in the inhibition of autophagy, leads to accelerated DN ( 110 ). Furthermore, Liang et al found that TP protects podocyte autophagy by suppressing the mTOR and AKT pathways in IgAN ( 56 ) ( Table 1 , Figures 2 , 3 ).…”