Table 2 Potential approaches to target podocyte death in DKD
From: Research progress on multiple cell death pathways of podocytes in diabetic kidney disease
Mode of cell death | Treatment | Mechanism of action | DKD model | References |
|---|---|---|---|---|
Apoptosis | TXNIP gene was deleted | Termination of O2− production in mitochondria and inhibition of oxidative stress | STZ-induced TxNIP WT (TxNIP), TxNIP KO (TxNIP+/+−/−), TxNIP HET (TxNIP+/−), and Hcb-19 mice Hg-induced conditionally immortalized human podocytes | Shah et al. (2015) |
Sestrin2 was overexpressed | Inhibition of the TSP-1/TGF-β1/Smad3 pathway inhibits oxidative stress | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | Shan et al. (2015) | |
ADSC-Exo | The Smad1/mTOR pathway was inhibited by enhancing miR-486 expression | C0010BL/KsJ db/db mice Hg-induced MPC5 cells | Jin et al. (2019) | |
Telmisartan | Inhibition of swiprosin-1 expression further inhibited the p38 MAPK pathway | STZ-induced Sprague–Dawley rats Hg-induced MPC5 cells | Wei et al. (2022) | |
Wogonin | Enhanced anti-apoptotic Bcl-2 activation | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | ||
AS-IV | Activation of PPARγ-Klotho-FoxO1 pathway inhibits oxidative stress | C57BLKS/J-LepR db/db mice Hg-induced MPC5 cells | Xing et al. (2021) | |
Autophagy | Down-regulation of Risa | Inhibition of the Sirt1/GSK3β pathway | C57BL/KsJ db/db mice Hg-induced MPC5 cells | Su et al. (2022) |
PGRN | Enhanced PGRN-Sirt1-PGC-1α/FoxO1 pathway | STZ-induced C57BL/6 mice | Zhou et al. (2019) | |
BBR | Inhibition of the mTOR/P70S6K/4EBP1 pathway | Hg-induced MPC5 cells | Li et al. (2020) | |
Mangiferin | It promoted the up-regulation of AMPK phosphorylation, the down-regulation of mTOR phosphorylation, and the up-regulation of p-ULK1 | STZ-induced Sprague–Dawley rats Hg-induced MPC5 cells | Wang et al. (2018) | |
JTBF | Inhibition of the PI3K/Akt/mTOR pathway | STZ-induced Sprague–Dawley rats | Jin et al. (2022) | |
NR1 | Activation of the PI3K/Akt pathway | Hg-induced conditionally immortalized human podocytes | Huang et al. (2017) | |
Geniposide | Enhanced AMPK activity | STZ-induced C57BL/6 mice | Dusabimana et al. (2021) | |
ER stress | LINC01619 | Inhibition of the miR-27a/FOXO1 pathway | STZ-induced Sprague–Dawley rats Hg-induced MPC5 cells | Bai et al. (2018) |
TUDCA | It inhibits the expression of ER stress markers | C57BL/KsJ db/db mice Hg-induced conditionally immortalized human podocytes | ||
Emodin | Inhibition of the PERK-eIF2α pathway | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | Tian et al. (2018) | |
OA | Enhance antioxidant effect | C57BL/KsJ db/db mice | Lee et al. (2016) | |
NAC | Enhance antioxidant effect | C57BL/KsJ db/db mice | Lee et al. (2016) | |
Unsaturated free fatty acids | Attenuate the upregulation of CHOP | Hg-induced MPC5 cells | Sieber et al. (2010) | |
Pyroptosis | Gene therapy for IL-22 | Inhibition of NLRP3 inflammasome activation | STZ-induced C57BL/6 mice | Wang et al. (2017) |
Inhibition of MiR-21-5p in macrophage-derived EVs | It also reduced the levels of NLRP3, caspase-1, and IL-1β, which are inflammasomes associated with pyroptosis | STZ-induced C57BL/6 mice Hg-induced MPC5 cells | Ding et al. (2021) | |
Knockdown of caspase-11 or GSDMD | Inhibition of caspase-11 and GSDMD-mediated pyroptosis | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | Cheng et al. (2021) | |
SS | Inhibition of the Nrf2/NLRP3 pathway | Hg-induced MPC5 cells | Zhang et al. (2022) | |
TFA | Targeting m6A modifation-mediated NLRP3 inflammasome activation and the PTEN/PI3K/Akt pathway | Hg-induced MPC5 cells | Liu et al. (2021) | |
FPS | Regulating the AMPK/mTORC3/NLRP1 pathway inhibits the activation of NLRP3 inflammasome | STZ-induced Sprague–Dawley rats Hg-induced MPC5 cells | ||
Carnosine | Targeting caspase-1 | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | Zhu et al. (2021) | |
Necroptosis | The UCHL1 gene was deleted | This results in a shortened half-life of RIPK1 and RIPK3 proteins and a decrease in their expression | Hg-induced MPC5 cells | Xu et al. (2019) |
Nec1 | The expression of RIPK1 and RIPK3 was inhibited | Hg-induced MPC5 cells | Xu et al. (2019) | |
PF | It directly binds and promotes the degradation of TNFR1 in podocytes, thereby inhibiting the RIPK1/RIPK3 pathway | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | ||
Curcumin | Inhibition of ROS production and abnormal expression of RIPK3 | Hg-induced MPC5 cells | Chung et al. (2022) | |
Ferroptosis | The expression of Prdx6 was up-regulated | Alleviates oxidative stress | STZ-induced C57BL/6 mice Hg-induced MPC5 cells | Zhang et al. (2022) |
Rosiglitazone | Inhibition of ACSL4 expression reduces lipid peroxidation | STZ-induced ICR mice C57BL/KsJ db/db mice | Wang et al. (2021) | |
GB | Inhibition of GPX4 ubiquitination | C57BL/KsJ db/db mice Hg-induced MPC5 cells | Chen et al. (2022) | |
MGM | Up-regulation of mevalonate-mediated antioxidant capacity and impairment of ACSL4-mediated lipid driver production in the kidney | STZ-induced Sprague–Dawley rats | Zhao et al. (2023) | |
Mitotic catastrophe | Inhibition of lncRNA MIAT | It increases the expression of Sox4, which in turn regulates p53 ubiquitination and acetylation | STZ-induced C57BL/6 mice | |
MYDGF | Activation of the Akt/BAD pathway | STZ-induced C57BL/6J mice Hg-induced MPC5 cells | He et al. (2020) |