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已发表论文
单细胞测序揭示了在糖尿病肾病中驱动肾纤维化的表达 TMSB10 的成纤维细胞亚群
Authors Qin Z , Huang X , Du K , Zhang L , Xu X , Fang Y
Received 5 September 2025
Accepted for publication 13 December 2025
Published 31 December 2025 Volume 2025:18 Pages 4913—4929
DOI https://doi.org/10.2147/DMSO.S559695
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Rebecca Baqiyyah Conway
Zihan Qin,1 Xiaoli Huang,2 Ke Du,3 Liexiang Zhang,4 Xiaohong Xu,5 Yuepeng Fang6
1Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, People’s Republic of China; 3Department of Endocrinology and Metabolism, Jurong People’s Hospital, Jiangsu University, Zhenjiang, People’s Republic of China; 4Department of Neurosurgery, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, People’s Republic of China; 5Department of Nephrology, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, People’s Republic of China; 6Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China
Correspondence: Xiaohong Xu, Email amfeiyang@126.com Yuepeng Fang, Email fangyuepeng163@163.com
Introduction: Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease (ESKD), with renal fibrosis as a key pathological hallmark. However, the cellular and molecular drivers of fibrosis remain incompletely defined. Here, we employed single-cell RNA sequencing (scRNA-seq) to delineate pro-fibrotic cell subsets and their key regulatory factors in human DN kidneys, providing a higher-resolution view compared to previous fibrosis-related scRNA-seq studies.
Methods: Publicly available scRNA-seq datasets from human DN and control kidneys were analyzed to identify fibrosis-associated fibroblast subsets. A Tmsb10-high fibroblast population was prioritized. Functional validation was performed through Tmsb10 knockdown in NIH-3T3 fibroblasts and in a diabetic mouse model, followed by assessment of fibrosis markers, extracellular matrix (ECM) deposition, and TGF-β/SMAD signaling.
Results: scRNA-seq revealed a significant expansion of Tmsb10-high fibroblasts in DN kidneys, exhibiting strong enrichment of ECM-related and TGF-β/SMAD-responsive genes. Tmsb10 knockdown reduced Fn1, Col1a1, and α-Sma expression by approximately 50– 70% and markedly attenuated ECM accumulation in vivo. Mechanistically, TMSB10 deficiency suppressed phosphorylation of SMAD2/3, mitigating fibroblast activation and matrix deposition.
Discussion: This study identifies TMSB10 as a novel fibroblast-specific regulator of renal fibrosis in DN, acting through the TGF-β/SMAD pathway. These findings expand current understanding of fibroblast heterogeneity and highlight TMSB10 as a potential therapeutic target for DN and other fibrotic diseases. Limitations include validation in a limited sample size and the use of murine fibroblast models, warranting further confirmation in human primary cells.
Keywords: diabetic nephropathy (DN), thymosin beta-10 (TMSB10), single-cell RNA sequencing (scRNA-seq), renal fibrosis, TGF/SMAD signaling pathway
1Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, People’s Republic of China; 3Department of Endocrinology and Metabolism, Jurong People’s Hospital, Jiangsu University, Zhenjiang, People’s Republic of China; 4Department of Neurosurgery, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, People’s Republic of China; 5Department of Nephrology, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, People’s Republic of China; 6Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China
Correspondence: Xiaohong Xu, Email amfeiyang@126.com Yuepeng Fang, Email fangyuepeng163@163.com
Introduction: Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease (ESKD), with renal fibrosis as a key pathological hallmark. However, the cellular and molecular drivers of fibrosis remain incompletely defined. Here, we employed single-cell RNA sequencing (scRNA-seq) to delineate pro-fibrotic cell subsets and their key regulatory factors in human DN kidneys, providing a higher-resolution view compared to previous fibrosis-related scRNA-seq studies.
Methods: Publicly available scRNA-seq datasets from human DN and control kidneys were analyzed to identify fibrosis-associated fibroblast subsets. A Tmsb10-high fibroblast population was prioritized. Functional validation was performed through Tmsb10 knockdown in NIH-3T3 fibroblasts and in a diabetic mouse model, followed by assessment of fibrosis markers, extracellular matrix (ECM) deposition, and TGF-β/SMAD signaling.
Results: scRNA-seq revealed a significant expansion of Tmsb10-high fibroblasts in DN kidneys, exhibiting strong enrichment of ECM-related and TGF-β/SMAD-responsive genes. Tmsb10 knockdown reduced Fn1, Col1a1, and α-Sma expression by approximately 50– 70% and markedly attenuated ECM accumulation in vivo. Mechanistically, TMSB10 deficiency suppressed phosphorylation of SMAD2/3, mitigating fibroblast activation and matrix deposition.
Discussion: This study identifies TMSB10 as a novel fibroblast-specific regulator of renal fibrosis in DN, acting through the TGF-β/SMAD pathway. These findings expand current understanding of fibroblast heterogeneity and highlight TMSB10 as a potential therapeutic target for DN and other fibrotic diseases. Limitations include validation in a limited sample size and the use of murine fibroblast models, warranting further confirmation in human primary cells.
Keywords: diabetic nephropathy (DN), thymosin beta-10 (TMSB10), single-cell RNA sequencing (scRNA-seq), renal fibrosis, TGF/SMAD signaling pathway