1:300), NQO1 (Proteintech; 67240-1-Ig, 1:2500), OLIG2 (Bio SB; BSB 2561, 1:200), p62 (Cell Signaling Technology; 39749, 1:400), PCK1 (Proteintech; 66862-1-Ig, 1:400), PCNA (Abcam; ab29, 1:2000), PDGFRβ (Cell Signaling Technology; 3169, 1:100), PDI (Cell Signaling Technology; 45596S, 1:400), Periostin (R&D Systems; AF3548, 1:150), Phospho-AMPKα (Cell Signaling Technology; 2535, 1:200), Phospho-c-Jun (Abcam; ab32385, 1:200), Phospho-Erk1/2 (Cell Signaling Technology; 4370, 1:250), Phospho-Ezrin/Radixin/Moesin (Cell Signaling Technology; 3726, 1:200), Phospho-GSK-3β (Cell Signaling Technology; 9323, 1:100), Phospho-Histone H3 (Cell Signaling Technology; 9701, 1:200), Phospho-JAK2 (Thermo Fisher Scientific; MA5-42424, 1:100), Phospho-S6 Ribosomal Protein (Cell Signaling Technology; 4858S, 1:300), Phospho-SMAD2 (Thermo Fisher Scientific; 44-244G, 1:200), Phospho-SMAD3 (Thermo Fisher Scientific; PA5-104940, 1:200), Phospho-STAT1 (Cell Signaling Technology; 9167S, 1:400), Phospho-STAT3 (Abcam; ab76315, 1:200), PITX2 (R&D Systems; AF7388, 1:100), Podocin (Sigma-Aldrich; P0372, 1:3000), Proteasome 20S LMP7 (Abcam; ab3329, 1:400), Rab5A (Cell Signaling Technology; 46449, 1:300), RAB7 (Abcam; ab137029, 1:200), RAP1GAP (Abcam; ab244259, 1:300), RCA51 (Cell Signaling Technology; 12290, 1:200), Sclerostin (Thermo Fisher Scientific; PA5-37943, 1:100), SirT1 (Cell Signaling Technology; 8469, 1:200), SLC12A3 (Thermo Fisher Scientific; MA5-41643, 1:200), SOD1 (Proteintech; 67480-1-Ig, 1:400), SOD2 (Thermo Fisher Scientific; PA5-30604, 1:300), SRB1 (Abcam; ab217318, 1:300), STAT2 (R&D Systems; MAB16661, 1:200), Survivin (Cell Signaling Technology; 2808, 1:300), Talin 1 (Abcam; ab71333, 1:200), TRPC6 (Abcam; ab233413, 1:200), Ubiquityl-Histone H2B (Cell Signaling Technology; 5546T, 1:200), Uromodulin (R&D Systems; AF5144, 1:300), Villin 1 (Abcam; ab52102, 1:200), Vimentin (Progen; GP53, 1:200), von Willebrand Factor (Agilent; A008229-2, 1:200), WT1 (Agilent; IS05530-2, 1:200), ZO-1 (Thermo Fisher Scientific; 61-7300, 1:250).

For mouse samples. ACE-2 (R&D Systems; AF933, 1:200), AIF (Cell Signaling Technology; 5318, 1:200), AKAP12 (Proteintech; 25199-1-AP, 1:600), ANXA3 (Sigma-Aldrich; HPA013398, 1:200), αSMA-FITC conjugate (Abcam; F3777, 1:800), Aquaporin 2 (Alomone labs; AQP-002, 1:400), Calreticulin (Abcam; ab92516, 1:300), Caspase 1 p20 (Thermo Fisher Scientific; PA5-99390, 1:200), CD3 (Abcam; ab1108, 1:200), CD4 (Abcam; ab183685, 1:200), CD41 (Thermo Fisher Scientific; PA5-79526, 1:500), CD42b (Abcam; ab227669, 1:100), CD44-Alexa Fluor 647 conjugate (Bio Legend; 103018, 1:200), CD45 (Cell Signaling Technology; 70257, 1:200), c-Fos (Abcam; ab190289, 1:600), Collagen I (Southern Biotech; 1310-01, 1:200), Collagen IV (Abcam; ab6586, 1:200), Cytochrome C (Abcam; ab110325, 1:200), DACH1 (Sigma-Aldrich; HPA012672, 1:200), E-Cadherin (R&D Systems; AF648, 1:200), Endomucin (Santa Cruz; sc-65495, 1:200), Fibronectin (Abcam; ab2413, 1:200), Histone H3 (Cell Signaling Technology; 4499, 1:400), IBA1 (Thermo Fisher Scientific; MA5-27726, 1:500), IL-1RA (Abcam; ab124962, 1:200 - specificity issues were raised by the provider after our experiments were completed. We have kept it in the panel as none of our findings were affected and we did not perform any biological inferences based on this antibody), Ki67 (Abcam; ab15580, 1:200), Lamin B1 (Santa Cruz; sc-374015, 1:200), Laminin (Abcam; ab11575, 1:200), LTL biotinylated (Vector Laboratories; B-1325-2, 1:500), Nephrin (Progen; GP-N2, 1:150), PCNA (Abcam; ab29, 1:2000), PDI (Cell Signaling Technology; 45596S, 1:400), Phospho-Ezrin/Radixin/Moesin (Cell Signaling Technology; 3726, 1:200), Podocin (Sigma-Aldrich; P0372, 1:3000), Podoplanin (R&D Systems; AF3244-SP, 1:200), Synaptopodin (Synaptic Systems; 163 004, 1:200), Tyrosine Hydroxylase (Cell Signaling Technology; 45648, 1:200), Ubiquityl-Histone H2B (Cell Signaling Technology; 5546T, 1:200), β-Actin (Sigma-Aldrich; A5441, 1:1500), Vimentin (Progen; GP53, 1:200), von Willebrand Factor (Agilent; A008229-2, 1:200).

### Secondary antibodies and biotin-binding proteins

Secondary antibodies were diluted in a ratio ranging from 1:200 to 1:300. Antibodies: goat anti-guinea pig IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-11073), goat anti-guinea pig IgG Alexa Fluor 555 (Thermo Fisher Scientific; A-21435), donkey anti-mouse IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-21202), donkey anti-mouse IgG Alexa Fluor 555 (Thermo Fisher Scientific; A-31570), donkey anti-mouse IgG Alexa Fluor 647 (Thermo Fisher Scientific; A-31571), donkey anti-rabbit IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-21206), donkey anti-rabbit IgG Alexa Fluor 555 (Thermo Fisher Scientific; A-31572), donkey anti-rabbit IgG Alexa Fluor 647 (Thermo Fisher Scientific; A-31573), donkey anti-goat IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-11055), donkey anti-goat IgG Alexa Fluor 555 (Thermo Fisher Scientific; A-21432), donkey anti-rat IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-21208), donkey anti-rat IgG Alexa Fluor 555 (Thermo Fisher Scientific; A78945), donkey anti-sheep IgG Alexa Fluor 488 (Thermo Fisher Scientific; A-11015), donkey anti-sheep IgG Alexa Fluor 555 (Thermo Fisher Scientific; A-21436), streptavidin Alexa Fluor 488 (Thermo Fisher Scientific; S11223), streptavidin Alexa Fluor 555 (Thermo Fisher Scientific; S21381).

### Validation

To ensure that antibodies were validated and their staining quality was reliable, we relied on multiple levels of evidence. These include vendor specifications (i.e. recommended concentrations), the absence of primary antibody after elution steps, established staining patterns for every included antibody in the scientific literature, and references to available data from the Human Protein Atlas. These quality control steps were performed by at least 3 different team members. This process was repeated for every antibody included in this study. We provide confirmation of each staining pattern for every antibody in Supplementary Data 1 and 2.

## Eukaryotic cell lines

Policy information about **cell lines and Sex and Gender in Research**

Cell line source(s)

The parietal epithelial cell (PEC) line was provided by A/Prof. Olivia Lenoir and Prof. Pierre-Louis Tharaux

Authentication

In order to preserve their identity, all cell lines were maintained at low passages. This practice ensures consistency in the characteristics and behavior of the cells.

Mycoplasma contamination

It was confirmed that all cell lines were free of any contamination of mycoplasma.

Commonly misidentified lines
(See ICLAC register)

No commonly misidentified cell lines were used in this study.

## Animals and other research organisms

Policy information about **studies involving animals; ARRIVE guidelines** recommended for reporting animal research, and **Sex and Gender in Research**

Laboratory animals

All experimental animals were housed at ambient temperature of 20±2°C, humidity of 55±10% and a light/dark cycle of 12h/12h. Archival tissues from 8-12 week old C57BL/6J mice were used for the experimental glomerulonephritis experiment.
<table><tr><td></td><td>10-12 week-old Sprague Dawley rats were used for prevention experiments with JNK inhibitors, and Wister Kyoto (WKY) rats were used for therapeutic experiments. 12 and 24-week old BTBR-Lepob/ob (BTBRob/ob) mice were used as DKD model.</td></tr><tr><td>Wild animals</td><td>This study did not involve any wild animals.</td></tr><tr><td>Reporting on sex</td><td>All studies were performed in male rodents as kidney disease is more severe in males and our aim was to maximize pathological effects and potential interventions.</td></tr><tr><td>Field-collected samples</td><td>This study did not involve any samples collected from the field.</td></tr><tr><td>Ethics oversight</td><td>All animal experimental protocols were approved by the respective IRB in Hamburg, Melbourne (N047/20 and MMCB/2006/29), Paris (358-86/609EEC) and Heidelberg (H2052-2071/23)</td></tr></table>

Note that full information on the approval of the study protocol must also be provided in the manuscript.

## Plants

<table><tr><td>Seed stocks</td><td>Not applicable</td></tr><tr><td>Novel plant genotypes</td><td>Not applicable</td></tr><tr><td>Authentication</td><td>Not applicable</td></tr></table>