Wnt signaling in kidney: the initiator or terminator?
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REVIEW
Wnt signaling in kidney: the initiator or terminator? Ping Meng 1,2 & Mingsheng Zhu 3 & Xian Ling 1 & Lili Zhou 1,4 Received: 31 March 2020 / Revised: 14 August 2020 / Accepted: 8 September 2020 # The Author(s) 2020
Abstract The kidney is a key organ in the human body that excretes toxins and sustains the water–electrolyte balance. During embryonic development and disease progression, the kidney undergoes enormous changes in macrostructure, accompanied by a variety of microstructural histological changes, such as glomerular formation and sclerosis, tubule elongation and atrophy, interstitial establishment, and fibrosis progression. All of these rely on the frequent occurrence of cell death and growth. Notably, to overcome disease, some cells regenerate through self-repair or progenitor cell differentiation. However, the signaling mechanisms underlying kidney development and regeneration have not been elucidated. Recently, Wnt signaling has been noted to play an important role. Although it is a well-known developmental signal, the role of Wnt signaling in kidney development and regeneration is not well recognized. In this review, we review the role of Wnt signaling in kidney embryonic development, tissue repair, cell division, and progenitor cell differentiation after injury. Moreover, we briefly highlight advances in our understanding of the pathogenic mechanisms of Wnt signaling in mediating cellular senescence in kidney parenchymal and stem cells, an irreversible arrest of cell proliferation blocking tissue repair and regeneration. We also highlight the therapeutic targets of Wnt signaling in kidney diseases and provide important clues for clinical strategies. Keywords Wnt . Kidney . Development . Regeneration . Senescence
Introduction The kidney is a key organ in the human body that removes toxins and metabolic wastes by excreting urine. In addition, the kidney executes filtration and reabsorption, has endocrinal functions to regulate water–electrolyte balance, stabilize blood pressure, boost erythropoiesis, and promote bone formation and growth. Although weighing only about 0.5% of the total body weight, the kidney’s blood distribution occupies Ping Meng and Mingsheng Zhu contributed equally to this work. * Lili Zhou [email protected] 1
State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou 510515, China
2
Department of Nephrology, Huadu District People’s Hospital, Southern Medical University, Guangzhou, China
3
Department of Nephrology, The People’s Hospital of Gaozhou, Maoming, China
4
Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
over 20% of the cardiac input [1]. To accomplish its tasks satisfactorily, the embryonic kidney develops extremely complex structures, including the nephron, peritubular capillary plexus, and interstitium [2]. Even though each kidney has a compensated brother, the kidney is sti
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