Histone deacetylase 6 suppression of renal tubular epithelial cell promotes interstitial mineral deposition via alpha-tubulin acetylation.

Autor: Li S; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China., Wu W; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China., Yang B; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China., Liu Z; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China., Duan X; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China., Sun X; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China., Liu H; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China., Zhang S; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China., Zhou Y; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China., Wu W; Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute Of Urology, Guangzhou, Guangdong 510230, China; Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China. Electronic address: 2009681012@gzhmu.edu.cn.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2024 Apr; Vol. 116, pp. 111057. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1016/j.cellsig.2024.111057
Abstrakt: Randall's plaque (RP) is derived from interstitial mineral deposition and is highly prevalent in renal calcium oxalate (CaOx) stone disease, which is predictive of recurrence. This study shows that histone deacetylase 6 (HDAC6) levels are suppressed in renal tubular epithelial cells in RP samples, in kidney tissues of hyperoxaluria rats, and in hyper-oxalate-treated or mineralized cultured renal tubular epithelial (MDCK) cells in vitro. Mineral deposition in MDCK cells was exacerbated by HDAC6 inhibition but alleviated by HDAC6 overexpression. Surprisingly, the expression of some osteogenic-associated proteins, were not increased along with the increasing of mineral deposition, and result of single-cell RNA sequencing of renal papillae samples revealed that epithelial cells possess lower calcific activity, suggesting that osteogenic-transdifferentiation may not have actually occurred in tubular epithelial cells despite mineral deposition. The initial mineral depositions facilitated by HDAC6 inhibitor were localized in extracellular dome rather than inside the cells, moreover, suppression of HDAC6 significantly increased the calcium content of co-cultured renal interstitial fibroblasts (NRK49F) and enhanced mineral deposition of indirectly co-cultured NRK49F cells, suggesting that HDAC6 may influence trans-MDCK monolayer secretion of mineral. Further experiments revealed that this regulatory role was partially alpha-tubulin Lys40 acetylation dependent. Collectively, these results suggest that hyper-oxalate exposure led to HDAC6 suppression in renal tubular epithelial cells, which may contribute to interstitial mineral deposition by promoting alpha-tubulin Lys40 acetylation. Therapeutic agents that influence HDAC6 activity may be beneficial in preventing RP and CaOx stone formation.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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