Effects of tacrolimus on autophagy protein LC3 in puromycin-damaged mouse podocytes

Yang, Xiaoqing; Yu, Shengyou; Yu, Li; Ge, Lin; Zhang, Yao; Hao, Zhihong; Liu, Guosheng

doi:10.1177/0300060520971422

Cited by 8 publications

(4 citation statements)

References 26 publications

(32 reference statements)

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“…Tacrolimus minimizes renal tissue damage by inhibiting the expression of transient receptor potential cation channel-6 (TRPC6) and impeding T cell activation. Podocytes cultured independently in a 2D environment and subjected to puromycin-induced injury showed enhanced autophagy after tacrolimus treatment by increasing the expression of microtubule-associated proteins 1A/1B light chain 3A (LC3), thereby preventing renal damage [ 25 ]. In rodent models of PAN-induced podocyte injury, the administration of tacrolimus confirmed the restoration of podocyte foot processes.…”

Section: Discussionmentioning

confidence: 99%

Development of Drug Efficacy Testing Platform for Glomerulonephritis

Kwon,

Choi,

Kim

et al. 2024

Micromachines

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We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples.

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Section: Discussionmentioning

confidence: 99%

Development of Drug Efficacy Testing Platform for Glomerulonephritis

Kwon,

Choi,

Kim

et al. 2024

Micromachines

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“…Xie and Yu ( 38 ) reported that the mitochondrial autophagy process mediated by the PINK1/Parkin signaling pathway is affected by a number of other proteins and related signaling pathways at the same time, so as to protect podocytes from external damage. Yang et al ( 39 ) revealed that by increasing the expression of autophagy-related protein LC3 and enhancing the autophagy activity of glomerular podocytes, they can significantly reduce the damage to glomerular podocytes in mice induced by puromycin, reduce the production of proteinuria and delay glomerular sclerosis. These findings suggest that increasing autophagy may be an effective protective mechanism of podocytes under the condition of injury.…”

Section: Discussionmentioning

confidence: 99%

Effects of DJ‑1 on apoptosis and mitophagy of glomerular podocytes

Xiao

Tan

et al. 2023

Exp Ther Med

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By studying the effects of DJ-1 overexpression and silencing on the morphological structure and mitophagy of glomerular podocytes, the present study aimed to identify the effects of DJ-1 on glomerular podocyte apoptosis and mitophagy. MPC5 mouse glomerular podocytes were cultured in vitro and divided into four groups: Control, DJ-1 overexpression, empty vector and DJ-1 silencing. DJ-1 gene overexpression and silencing models were prepared, the morphological structures of podocytes and mitochondria in each group were observed, and podocyte apoptosis and DJ-1/PTEN expression were subsequently detected in each group. The experimental results showed reduced volume, retracted foot processes, loosened intercellular connections, presence of dead cells, increased apoptotic rate, increased expression of PTEN, and swollen mitochondria due to the number of vacuoles and autophagosomes in podocytes in the DJ-1 silencing group. The surface areas of podocytes in the DJ-1 overexpression group were greater than those in the control group. Moreover, the structure of the foot processes was more obvious, the number of cells was greater, the intercellular connections were closer, the apoptotic rate was reduced, the expression of PTEN was decreased, the mitochondrial structure was more obvious and the mitochondrial cristae were more whole. Notably, there were no differences between the empty vector and control groups. In conclusion, these results indicated that DJ-1 may regulate podocyte apoptosis and mitophagy through the DJ-1/PTEN pathway, and could maintain the stability of the normal morphology, structure and function of glomerular podocytes.

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“…TAC also enhanced the interaction of FKBP12 with actin-associated proteins 14-3-3β and synaptopodin to maintain F-actin [ 171 ]. Moreover, TAC significantly improved the expression of nephrin and podocin in diabetic rats [ 172 ] and maintained the microtubule-associated protein 1 light chain 3 alpha (LC3) expression in PAN-induced podocyte injury [ 173 ]. In clinical settings, CNIs were effective in FSGS [ 174 ] and lupus podocytopathy cases [ 175 ].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Cytoskeleton Rearrangement in Podocytopathies: An Update

Ma,

Qiu,

Zhang

2024

IJMS

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Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus’s key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton.

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Effects of tacrolimus on autophagy protein LC3 in puromycin-damaged mouse podocytes

Cited by 8 publications

References 26 publications

Development of Drug Efficacy Testing Platform for Glomerulonephritis

Development of Drug Efficacy Testing Platform for Glomerulonephritis

Effects of DJ‑1 on apoptosis and mitophagy of glomerular podocytes

Cytoskeleton Rearrangement in Podocytopathies: An Update

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