Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
Cell Signal. 2024 Oct;122:111347. doi: 10.1016/j.cellsig.2024.111347. Epub 2024 Aug 13.
Chronic Kidney Disease (CKD) has emerged as a global public health concern, with its primary pathological basis being Renal Fibrosis (RF), crucial to halt its progression to End-Stage Renal Disease (ESRD). However, effective treatment options are currently lacking. Therefore, exploring the mechanisms of RF, identifying drug targets and diagnostic biomarkers are important. In this study, we identified ADAMTS16 as a newly expressed regulatory factor highly expressed in renal fibrosis tissue. ADAMTS16 interacts with latency-associated peptide (LAP)-transforming growth factor (TGF)-β, leading to the activation of TGF-β. Loss of ADAMTS16 expression effectively reduces TGF-β-dependent transcription activity. Furthermore, the use of RRFR tetrapeptide derived from ADAMTS16 can activate the TGF-β/Smad signaling axis, promoting RF. In summary, ADAMTS16 is induced in the progression of CKD, interacting with LAP-TGF-β and potentially activating SMAD2/3. Therefore, targeting ADAMTS16 may serve as a crucial new strategy to alleviate RF and treat CKD patients.
慢性肾脏病（CKD）已成为全球公共卫生关注的焦点，其主要的病理学基础是肾纤维化（RF），这对于阻止其进展为终末期肾病（ESRD）至关重要。然而，目前缺乏有效的治疗选择。因此，探索 RF 的机制，确定药物靶点和诊断生物标志物非常重要。在这项研究中，我们发现 ADAMTS16 是一种在肾纤维化组织中高表达的新表达调节因子。ADAMTS16 与潜伏相关肽（LAP）-转化生长因子（TGF）-β相互作用，导致 TGF-β的激活。ADAMTS16 表达的缺失可有效降低 TGF-β依赖性转录活性。此外，源自 ADAMTS16 的 RRFR 四肽可激活 TGF-β/Smad 信号通路，促进 RF。总之，ADAMTS16 在 CKD 的进展中被诱导，与 LAP-TGF-β相互作用，并可能激活 SMAD2/3。因此，靶向 ADAMTS16 可能是缓解 RF 和治疗 CKD 患者的重要新策略。
