Finerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy DOI Creative Commons
Zihan Li,

Zi‐Jun Sun,

Sydney C.W. Tang

и другие.

Cells, Год журнала: 2025, Номер 14(5), С. 337 - 337

Опубликована: Фев. 26, 2025

Diabetic nephropathy (DN), one of the most common complications diabetes mellitus (DM), accounts for a major cause chronic kidney disease (CKD) worldwide, with complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is classical ligand-activated nuclear transcription factor. It expressed in renal intrinsic immune cells, especially macrophages. Over-activation MR was observed patients DN associated prognosis. renoprotective role new generation non-steroidal selective antagonist (MRA), finerenone, has been confirmed DM CKD patients. However, mechanism by which finerenone improves inflammation yet to be completely understood. found this research that oral administration attenuated injuries established db/db mice, particularly improved pathological changes tubulointerstitia. Specifically, inhibited over-activation macrophages, thereby reducing expression G protein subunit alpha i2 (GNAI2, Gnαi2), key downstream component C5aR1 pathway. Animal experiments demonstrated knockout alleviated injuries, confirming critical pathogenic DN. Moreover, mitigated inflammatory chemotaxis responses downregulating Gnαi2 These effects were reflected reduced expressions pro-inflammatory chemokines CXCL15 CCL2, regulation macrophage polarization improvements apoptosis. This study intends understand protective DN, conducive revealing pathophysiological further optimizing treatment

Язык: Английский

Finerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy DOI Creative Commons
Zihan Li,

Zi‐Jun Sun,

Sydney C.W. Tang

и другие.

Cells, Год журнала: 2025, Номер 14(5), С. 337 - 337

Опубликована: Фев. 26, 2025

Diabetic nephropathy (DN), one of the most common complications diabetes mellitus (DM), accounts for a major cause chronic kidney disease (CKD) worldwide, with complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is classical ligand-activated nuclear transcription factor. It expressed in renal intrinsic immune cells, especially macrophages. Over-activation MR was observed patients DN associated prognosis. renoprotective role new generation non-steroidal selective antagonist (MRA), finerenone, has been confirmed DM CKD patients. However, mechanism by which finerenone improves inflammation yet to be completely understood. found this research that oral administration attenuated injuries established db/db mice, particularly improved pathological changes tubulointerstitia. Specifically, inhibited over-activation macrophages, thereby reducing expression G protein subunit alpha i2 (GNAI2, Gnαi2), key downstream component C5aR1 pathway. Animal experiments demonstrated knockout alleviated injuries, confirming critical pathogenic DN. Moreover, mitigated inflammatory chemotaxis responses downregulating Gnαi2 These effects were reflected reduced expressions pro-inflammatory chemokines CXCL15 CCL2, regulation macrophage polarization improvements apoptosis. This study intends understand protective DN, conducive revealing pathophysiological further optimizing treatment

Язык: Английский

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