PULMONARY PHARMACOLOGY & THERAPEUTICS
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2024
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IF 3.3
Huijuan Zhang,Jianli Qiu,Qianyi Zhao,Yong Zhang,Haitao Zheng,Ziying Dou,Yongbin Yan
Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro . Meanwhile, the protein content of TGF-β1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-β1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-β/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.
研究领域:
药理学
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肺病学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
FASEB JOURNAL
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2026
·Vol. 40
·期 1
·e71412
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IF 4.2
Bo Pang,Yan Zhang,Yikai Bai,Siyuan Chen,Zhida Wang
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes characterized by demyelination and axonal degeneration, yet effective therapies remain limited. This study investigates the role of Zinc finger and BTB domain-containing 16 (ZBTB16) in myelin damage during DPN. We identified that ZBTB16 was significantly elevated in sciatic nerves of streptozotocin (STZ)-induced diabetic mice via mRNA sequencing. In vivo, adeno-associated virus (AAV9)-mediated overexpression of ZBTB16 under the myelin protein zero (MPZ) promoter improved motor nerve conduction velocity and sensory nerve action potential, reduced demyelination and suppressed the expression of Schwann cell dedifferentiation markers (p-cJUN, p75NTR) while enhancing myelin markers (MBP, P0). ZBTB16 also ameliorated oxidative stress (restoring GSH/GSSG ratio, reducing ROS) and mitochondrial dysfunction (normalizing ATP/mtDNA levels, electron transport chain complexes I–IV). In vitro, ZBTB16 overexpression in high glucose (HG)-treated Schwann cells inhibited apoptosis, dedifferentiation, and mitochondrial defects. Mechanistically, ZBTB16 transcriptionally activated PTCD1 (a mitochondrial regulator) by binding its promoter, confirmed via dual-luciferase assays. Knockdown of PTCD1 abolished ZBTB16's protective effects on Schwann cell differentiation and mitochondrial function. These findings demonstrated that ZBTB16 attenuates DPN by maintaining mitochondrial integrity via PTCD1 activation, thereby inhibiting Schwann cell dedifferentiation and myelin loss. Our study suggests ZBTB16 as a promising target for ameliorating DPN-associated myelin injury. Graphical Schematic diagram of the mechanism of ZBTB16 to improve myelin damage in DPN. ZBTB16 protects the mitochondrial function of Schwann cells by promoting PTCD1 transcriptional activation and up-regulating PTCD1 expression, thereby maintaining the differentiation state of Schwann cells and preventing myelin damage during the progression of DPN.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
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IF 10.6
Lu Liu,Nan Zhou,Songning Fu,Linlin Wang,Yadong Liu,Changfeng Fu,Feng Xu,Weiying Guo,Yanhua Wu,Jin Cheng,Jun Dai,Yipeng Wang,Xiaofeng Wang,Qiwei Yang,Yuanyi Wang
The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as “osteogenesis-angiogenesis coupling”, which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 ( ZBTB16 ) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair. Graphical
研究领域:
细胞生物学
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再生医学
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骨科
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DOI
PubMed
高影响因子
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