Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy

Abstract Diabetic kidney disease (DKD), one of the most prevalent microvascular complications of diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in the deterioration of renal cells such as podocytes and tubular epithelial cells. Programmed cell dea...

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Main Authors: Fengzhao Liu, Zhenyu Yang, Jixin Li, Tao Wu, Xiangyu Li, Lijuan Zhao, Wenru Wang, Wenfei Yu, Guangheng Zhang, Yunsheng Xu
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Molecular Medicine
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Online Access:https://doi.org/10.1186/s10020-024-01020-5
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author Fengzhao Liu
Zhenyu Yang
Jixin Li
Tao Wu
Xiangyu Li
Lijuan Zhao
Wenru Wang
Wenfei Yu
Guangheng Zhang
Yunsheng Xu
author_facet Fengzhao Liu
Zhenyu Yang
Jixin Li
Tao Wu
Xiangyu Li
Lijuan Zhao
Wenru Wang
Wenfei Yu
Guangheng Zhang
Yunsheng Xu
author_sort Fengzhao Liu
collection DOAJ
description Abstract Diabetic kidney disease (DKD), one of the most prevalent microvascular complications of diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in the deterioration of renal cells such as podocytes and tubular epithelial cells. Programmed cell death (PCD), comprising apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, represents a spectrum of cell demise processes intricately governed by genetic mechanisms in vivo. Under physiological conditions, PCD facilitates the turnover of cellular populations and serves as a protective mechanism to eliminate impaired podocytes or tubular epithelial cells, thereby preserving renal tissue homeostasis amidst hyperglycemic stress. However, existing research predominantly elucidates individual modes of cell death, neglecting the intricate interplay and mutual modulation observed among various forms of PCD. In this comprehensive review, we delineate the diverse regulatory mechanisms governing PCD and elucidate the intricate crosstalk dynamics among distinct PCD pathways. Furthermore, we review recent advancements in understanding the pathogenesis of PCD and explore their implications in DKD. Additionally, we explore the potential of natural products derived primarily from botanical sources as therapeutic agents, highlighting their multifaceted effects on modulating PCD crosstalk, thereby proposing novel strategies for DKD treatment.
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spelling doaj-art-3d9b3cf72e0741d2a79800ec5476355f2024-12-22T12:32:13ZengBMCMolecular Medicine1528-36582024-12-0130115210.1186/s10020-024-01020-5Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapyFengzhao Liu0Zhenyu Yang1Jixin Li2Tao Wu3Xiangyu Li4Lijuan Zhao5Wenru Wang6Wenfei Yu7Guangheng Zhang8Yunsheng Xu9First College of Clinical Medicine, Shandong University of Traditional Chinese MedicineGraduate School of Heilongjiang University of Chinese MedicineXi Yuan Hospital, China Academy of Chinese Medical SciencesSchool of Traditional Chinese Medicine, Beijing University of Chinese MedicineWangjing Hospital, China Academy of Chinese Medical SciencesFirst College of Clinical Medicine, Shandong University of Traditional Chinese MedicineXi Yuan Hospital, China Academy of Chinese Medical SciencesFirst College of Clinical Medicine, Shandong University of Traditional Chinese MedicineFirst College of Clinical Medicine, Shandong University of Traditional Chinese MedicineDepartment of Endocrinology, Second Affiliated Hospital of Shandong University of Traditional Chinese MedicineAbstract Diabetic kidney disease (DKD), one of the most prevalent microvascular complications of diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in the deterioration of renal cells such as podocytes and tubular epithelial cells. Programmed cell death (PCD), comprising apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, represents a spectrum of cell demise processes intricately governed by genetic mechanisms in vivo. Under physiological conditions, PCD facilitates the turnover of cellular populations and serves as a protective mechanism to eliminate impaired podocytes or tubular epithelial cells, thereby preserving renal tissue homeostasis amidst hyperglycemic stress. However, existing research predominantly elucidates individual modes of cell death, neglecting the intricate interplay and mutual modulation observed among various forms of PCD. In this comprehensive review, we delineate the diverse regulatory mechanisms governing PCD and elucidate the intricate crosstalk dynamics among distinct PCD pathways. Furthermore, we review recent advancements in understanding the pathogenesis of PCD and explore their implications in DKD. Additionally, we explore the potential of natural products derived primarily from botanical sources as therapeutic agents, highlighting their multifaceted effects on modulating PCD crosstalk, thereby proposing novel strategies for DKD treatment.https://doi.org/10.1186/s10020-024-01020-5Diabetic kidney diseaseProgrammed cell deathNatural productsPodocytesTubular epithelial cells
spellingShingle Fengzhao Liu
Zhenyu Yang
Jixin Li
Tao Wu
Xiangyu Li
Lijuan Zhao
Wenru Wang
Wenfei Yu
Guangheng Zhang
Yunsheng Xu
Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
Molecular Medicine
Diabetic kidney disease
Programmed cell death
Natural products
Podocytes
Tubular epithelial cells
title Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
title_full Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
title_fullStr Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
title_full_unstemmed Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
title_short Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy
title_sort targeting programmed cell death in diabetic kidney disease from molecular mechanisms to pharmacotherapy
topic Diabetic kidney disease
Programmed cell death
Natural products
Podocytes
Tubular epithelial cells
url https://doi.org/10.1186/s10020-024-01020-5
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