Finerenone Modulates PANoptosis to Improve Immune Microenvironment in Diabetic Nephropathy: A Machine Learning–Based Mechanistic Analysis

Amazit L, Le Billan F, Kolkhof P et al (2015) Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J Biol Chem 290(36):21876–21889

CAS  PubMed  PubMed Central  Google Scholar 

Bakris GL, Agarwal R, Anker SD et al (2020) Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 383(23):2219–2229

CAS  PubMed  Google Scholar 

Barrera-Chimal J, Estrela GR, Lechner SM et al (2018) The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int 93(6):1344–1355

CAS  PubMed  Google Scholar 

Chen J, Liu Q, He J, Li Y (2022Aug) Immune responses in diabetic nephropathy: pathogenic mechanisms and therapeutic target. Front Immunol 15(13):958790

Google Scholar 

Chow F, Ozols E, Nikolic-Paterson DJ et al (2004) Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney Int 65(1):116–128

CAS  PubMed  Google Scholar 

Christgen S, Tweedell RE, Kanneganti TD (2022) Programming inflammatory cell death for therapy. Pharmacol Ther 232:108010

CAS  PubMed  Google Scholar 

De P, Khine MT, Frankel A, Goldet G, Banerjee D, Montero RM, Chowdhury TA, Fogarty D, Karalliedde J, Mallik R, Patel DC, Wahba M, Winocour P, Zac-Varghese S, Bain S, Sharif A, Bellary S, Dasgupta I (2025) Finerenone in the management of diabetes kidney disease. BMC Nephrol 26(1):63. https://doi.org/10.1186/s12882-025-03985-9.PMID:39923037;PMCID:PMC11807303

PubMed  PubMed Central  Google Scholar 

de Morais R B, do Couto Muniz V P, Costa E N, et al. Mast cell population in the development of diabetic nephropathy: effects of renin angiotensin system inhibition. Biomedicine & Pharmacotherapy, 2018, 107: 1115–1118

Fan Y, Yi Z, D’Agati VD et al (2019) Comparison of kidney transcriptomic profiles of early and advanced diabetic nephropathy reveals potential new mechanisms for disease progression. Diabetes 68(12):2301–2314

CAS  PubMed  PubMed Central  Google Scholar 

Feng S, McNehlan ME, Kinsella RL, Sur Chowdhury C, Chavez SM, Naik SK, McKee SR, Van Winkle JA, Dubey N, Samuels A, Swain A, Cui X, Hendrix SV, Woodson R, Kreamalmeyer D, Smirnov A, Artyomov MN, Virgin HW, Wang YT, Stallings CL (2024) Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice. Nat Microbiol 9(3):684–697

CAS  PubMed  Google Scholar 

Filippatos G, Pitt B, Agarwal R, Farmakis D, Ruilope LM, Rossing P, Bauersachs J, Mentz RJ, Kolkhof P, Scott C, Joseph A, Bakris GL, Anker SD (2022) FIDELIO-DKD Investigators. Finerenone in patients with chronic kidney disease and type 2 diabetes with and without heart failure: a prespecified subgroup analysis of the FIDELIO-DKD trial. Eur J Heart Fail 24(6):996–1005

Fuchs Y, Steller H (2015) Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol 16(6):329–344

CAS  PubMed  PubMed Central  Google Scholar 

Gao YM, Chen WJ, Deng ZL et al (2023) Association between triglyceride-glucose index and risk of end-stage renal disease in patients with type 2 diabetes mellitus and chronic kidney disease. Front Endocrinol 14:1150980

Google Scholar 

Ghosh S, Khazaei M, Moien-Afshari F et al (2009) Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice. American Journal of Physiology-Renal Physiology 296(4):F700–F708

CAS  PubMed  PubMed Central  Google Scholar 

Grune J, Beyhoff N, Smeir E et al (2018) Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension 71(4):599–608

CAS  PubMed  Google Scholar 

Guan Z, Jin X, Guan Z et al (2023) The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF-1α to inhibit knee osteoarthritis-induced ferroptosis. Aging Cell 22(6):e13807

CAS  PubMed  PubMed Central  Google Scholar 

Huang F, Wang Q, Guo F et al (2019) FoxO1-mediated inhibition of STAT1 alleviates tubulointerstitial fibrosis and tubule apoptosis in diabetic kidney disease. EBioMedicine 48:491–504

PubMed  PubMed Central  Google Scholar 

Ji L, Chen Y, Wang H et al (2019) Overexpression of Sirt6 promotes M2 macrophage transformation, alleviating renal injury in diabetic nephropathy. Int J Oncol 55(1):103–115

CAS  PubMed  PubMed Central  Google Scholar 

Jiang W, Deng Z, Dai X et al (2021) PANoptosis: a new insight into oral infectious diseases. Front Immunol 12:789610

CAS  PubMed  PubMed Central  Google Scholar 

Jourdan T, Park JK, Varga ZV et al (2018) Cannabinoid-1 receptor deletion in podocytes mitigates both glomerular and tubular dysfunction in a mouse model of diabetic nephropathy. Diabetes Obes Metab 20(3):698–708

CAS  PubMed  Google Scholar 

Karki R, Sharma BR, Banoth B et al (2020) Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer. JCI Insight 5(12):e136720

PubMed  PubMed Central  Google Scholar 

Karki R, Sharma B R, Tuladhar S, et al (2021) Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184(1): 149–168. e17

Kim HW, Lim JH, Kim MY, Chung S, Shin SJ, Chung HW, Choi BS, Kim YS, Chang YS, Park CW (2011) Long-term blockade of vascular endothelial growth factor receptor-2 aggravates the diabetic renal dysfunction associated with inactivation of the Akt/eNOS-NO axis. Nephrol Dial Transplant 26(4):1173–1188. https://doi.org/10.1093/ndt/gfq610

CAS  PubMed  Google Scholar 

Kolkhof P, Delbeck M, Kretschmer A et al (2014) Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 64(1):69–78

CAS  PubMed  Google Scholar 

Kong L, Andrikopoulos S, MacIsaac RJ, Mackay LK, Nikolic-Paterson DJ, Torkamani N, Zafari N, Marin ECS, Ekinci EI (2022) Role of the adaptive immune system in diabetic kidney disease. Journal of Diabetes Investigation 13(2):213–226. https://doi.org/10.1111/jdi.13725

PubMed  Google Scholar 

Lattenist L, Lechner SM, Messaoudi S et al (2017) Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury–mediated chronic kidney disease: role of oxidative stress. Hypertension 69(5):870–878

CAS  PubMed  Google Scholar 

Lattenist L, Lechner SM, Messaoudi S, Le Mercier A, El Moghrabi S, Prince S, Bobadilla NA, Kolkhof P, Jaisser F, Barrera-Chimal J (2017) Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury-mediated chronic kidney disease: role of oxidative stress. Hypertension 69(5):870–878

CAS  PubMed  Google Scholar 

Li RY, Guo L (2024) Exercise in diabetic nephropathy: protective effects and molecular mechanism. Int J Mol Sci 25(7):3605

CAS  PubMed  PubMed Central  Google Scholar 

Li P, Jiang M, Li K et al (2021) Glutathione peroxidase 4–regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol 22(9):1107–1117

CAS  PubMed  PubMed Central  Google Scholar 

Li J, Li L, Zhang Z et al (2023) Ferroptosis: an important player in the inflammatory response in diabetic nephropathy. Front Immunol 14:1294317

CAS  PubMed  PubMed Central  Google Scholar 

Lin YC, Chang YH, Yang SY et al (2018) Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc 117(8):662–675

CAS  PubMed  Google Scholar 

Lin J, Cheng A, Cheng K et al (2020) New insights into the mechanisms of pyroptosis and implications for diabetic kidney disease. Int J Mol Sci 21(19):7057

CAS  PubMed  PubMed Central  Google Scholar 

Liu P, Zhang Z, Li Y (2021a) Relevance of the pyroptosis-related inflammasome pathway in the pathogenesis of diabetic kidney disease. Front Immunol 12:603416

CAS  PubMed  PubMed Central  Google Scholar 

Liu X, Xia S, Zhang Z et al (2021b) Channelling inflammation: gasdermins in physiology and disease. Nat Rev Drug Discovery 20(5):384–405

CAS  PubMed  Google Scholar 

Liu J, Hong M, Li Y et al (2022) Programmed cell death tunes tumor immunity. Front Immunol 13:847345

CAS  PubMed  PubMed Central  Google Scholar 

Malireddi RKS, Kesavardhana S, Kanneganti TD (2019) ZBP1 and TAK1: master regulators of NLRP3 inflammasome/pyroptosis, apoptosis, and necroptosis (PAN-optosis). Front Cell Infect Microbiol 9:406

CAS  PubMed  PubMed Central  Google Scholar 

Pan Y, Jiang S, Hou Q et al (2018) Dissection of glomerular transcriptional profile in patients with diabetic nephropathy: SRGAP2a protects podocyte structure and function. Diabetes 67(4):717–730

CAS  PubMed  Google Scholar 

Pitt B, Filippatos G, Agarwal R et al (2021) Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 385(24):2252–2263

CAS 

Comments (0)

No login
gif