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中国人群尿道狭窄疾病的综合蛋白质组学特征分析

Comprehensive proteomic characterization of urethral stricture disease in the Chinese population.

作者信息

Gao Jiangtao, Liu Hui, Li Lingling, Guo Chunmei, Wang Zhiyong, Cheng Mengya, Tan Subei, Chen Lu, Shi Jijing, Wu Hui, Feng Chao, Yu Guoying, Ding Chen

机构信息

Department of Urology, The First People's Hospital of Zhengzhou, Henan, China.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.

出版信息

Front Mol Biosci. 2024 Jul 26;11:1401970. doi: 10.3389/fmolb.2024.1401970. eCollection 2024.

DOI:10.3389/fmolb.2024.1401970
PMID:39130371
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310122/
Abstract

BACKGROUND

Male urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined.

METHODS

The proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs). Proteomic analysis methods were applied to explore the molecular characterizations of USD formation, including uncovering mechanistic pathways and providing novel biomarkers for scar formation.

RESULTS

Comparative proteomic analysis showed that the extracellular matrix (ECM) and complement cascade signaling were predominant in scar tissues. COL11A1 and CD248 significantly contributed to the accumulation of ECM components. Our study presented diverse molecular mechanisms of scar formation across different ages and suggested the potential effects of PXK in Age 1 (<45) patients. Furthermore, immune infiltration studies indicated the therapeutic potential of inhibiting the complement system (C4A, C4B) in Age 2 (≥45) patients, providing a potential clinical strategy for USD.

CONCLUSION

This study illustrated the pathogenesis of USD formation and the diverse characteristics of USD patients with different ages, enhancing our understanding of the disease's pathogenesis and providing a valuable resource for USD treatment.

摘要

背景

男性尿道狭窄疾病（USD）主要特征为瘢痕形成。有效的治疗药物很少，且USD形成的全面分子特征仍不明确。

方法

对12个瘢痕组织和5个匹配的正常相邻组织（NATs）进行蛋白质组分析。应用蛋白质组分析方法探索USD形成的分子特征，包括揭示机制途径和为瘢痕形成提供新的生物标志物。

结果

比较蛋白质组分析表明，细胞外基质（ECM）和补体级联信号在瘢痕组织中占主导地位。COL11A1和CD248对ECM成分的积累有显著贡献。我们的研究揭示了不同年龄瘢痕形成的多种分子机制，并提示了PXK在1龄（<45岁）患者中的潜在作用。此外，免疫浸润研究表明，在2龄（≥45岁）患者中抑制补体系统（C4A、C4B）具有治疗潜力，为USD提供了一种潜在的临床策略。

结论

本研究阐明了USD形成的发病机制以及不同年龄USD患者的多样特征，加深了我们对该疾病发病机制的理解，并为USD治疗提供了有价值的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/c68d55aebf16/fmolb-11-1401970-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/2625fa90797a/fmolb-11-1401970-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/5a2b4f4e084f/fmolb-11-1401970-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/fd9b5ac0eebf/fmolb-11-1401970-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/aa74973753f5/fmolb-11-1401970-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/d49ce9631712/fmolb-11-1401970-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/c68d55aebf16/fmolb-11-1401970-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/2625fa90797a/fmolb-11-1401970-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/5a2b4f4e084f/fmolb-11-1401970-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/fd9b5ac0eebf/fmolb-11-1401970-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/aa74973753f5/fmolb-11-1401970-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/d49ce9631712/fmolb-11-1401970-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63d/11310122/c68d55aebf16/fmolb-11-1401970-g006.jpg

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