A single-cell profile reveals the transcriptional regulation responded for Abelmoschus manihot (L.) treatment in diabetic kidney disease.

Autor: Wu C; Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, China; Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China., Tang H; Suzhong Pharmaceutical Research Institute, Nanjing, Jiangsu Province, 210018, China., Cui X; Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, China., Li N; Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210029, China., Fei J; Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China., Ge H; Suzhong Pharmaceutical Research Institute, Nanjing, Jiangsu Province, 210018, China., Wu L; Jiangsu Key Laboratory of Drug Screening, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, China., Wu J; Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China. Electronic address: wujie@cpu.edu.cn., Gu HF; Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, China. Electronic address: feng.gu@cpu.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jul 25; Vol. 130, pp. 155642. Date of Electronic Publication: 2024 May 10.
DOI: 10.1016/j.phymed.2024.155642
Abstrakt: Background: Huangkui capsule (HKC), as an ethanol extract of Abelmoschus manihot (L.), has a significant efficacy in treatment of the patients with diabetic kidney disease (DKD). The bioactive ingredients of HKC mainly include the flavonoids such as rutin, hyperoside, hibifolin, isoquercetin, myricetin, quercetin and quercetin-3-O-robinobioside.
Purpose: To explore the molecular mechanisms of A. manihot in treatment of DKD.
Study Design: A single-cell RNA sequencing analysis of kidneys in db/db mice with and without HKC administration.
Methods: Urinary biochemical and histopathological examination in C57BL/6 and db/db mice of DKD and HKC groups was done. Single-cell RNA sequencing pipeline was then performed. The regulatory mechanisms of seven flavonoids in HKC were revealed by cell communication, prediction of transcription factor regulatory network, and molecular docking.
Results: By constructing ligand-receptor regulatory network and performing molecular docking between 75 receptors with different activities and seven flavonoids. 11 key receptors in 4 cell types (segment 3 proximal convoluted tubular cell, ascending limbs of the loop of Henle, distal convoluted tubule, and T cell) in kidneys were found to be directly interacted with HKC. The interactions regulated 8 downstream regulons. The docking receptors in T cell led to transcriptional event differences in the regulons such as Cebpb, Rel, Tbx21 and Klf2 and consequently affected the activation, differentiation, and infiltration of T cell, while the receptors Tgfbr1 and Ldlr in stromal cells of kidneys were closely associated with the downstream transcriptional events of renal injury and proteinuria in DKD.
Conclusion: The current study provides novel information of the key receptors and regulons in renal cells for a better understanding of the cell type specific molecular mechanisms of A. manihot in treatment of DKD.
Competing Interests: Declaration of competing interest There are no potential conflicts of interest relevant to this article.
(Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE