Regenerative Therapy
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2025
·
IF 3.5
Yude Hong,Zejia Feng,Yunlong Ge,Yuhang Xi,Bowen Zhang,Jianjie Wu,Tian Xia,Bowen Tang,Wei Wang,Jun Chen,Hua Wang,Hengjun Xiao
Background Neurogenic erectile dysfunction (ED) is a prevalent complication following radical prostatectomy in elderly patients, primarily resulting from the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and the subsequent excessive fibrosis of the corpus cavernosum. Aim This study aimed to compare the therapeutic effects of exosomes derived from lentivirus-transfected miR-145 bone marrow mesenchymal stem cells (Exo-145) and unmodified BMSCs-derived exosomes (Exo) in aged rats with bilateral cavernous nerve injury (BCNI) and investigate the underlying mechanisms. Methods Twenty-four-month-old male rats were assigned to four groups, namely Sham, BCNI, Exo, and Exo-145. Three weeks after treatment, erectile function was assessed by measuring the maximal intracavernosal pressure to mean arterial pressure (ICP/MAP) ratio. Apoptosis and fibrosis were semi-quantitatively analyzed using TUNEL and Masson's trichrome staining, respectively. In vitro, CCSMCs were subjected to H 2 O 2 -induced oxidative stress, and the protective effects of Exo-145 were evaluated through flow cytometry and Western blot. Lastly, the targets and mechanisms of miR-145 were further validated using dual-luciferase reporter assays and rescue experiments. Results Exo-145 significantly outperformed Exo in restoring erectile function in aged BCNI rats, as evidenced by the significantly higher maximal ICP/MAP ratio, a marked reduction in TUNEL-positive cell count, and marked suppression of fibrosis in cavernous tissue. Moreover, Masson's trichrome staining displayed a substantial decrease in collagen deposition. In vitro, Exo-145 alleviated H 2 O 2 -induced apoptosis in CCSMCs by downregulating Cleaved Caspase-3 expression and Bax while concurrently upregulating Bcl-2 expression. TGFBR2 was identified as a direct target of miR-145 through dual-luciferase reporter assays, with its overexpression partially reversing the protective effects of Exo-145. Conclusion Exo-145 demonstrates superior efficacy compared to Exo in treating aged neurogenic ED by targeting TGFBR2 to alleviate apoptosis and fibrosis. It may represent a promising cell-free therapeutic option for neurogenic erectile dysfunction in elderly patients and could offer new perspectives for improving their prognosis.
研究领域:
男科学
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分子生物学
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干细胞研究
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老年医学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2026
·Vol. 107
·期 3
·e70264
·
IF 3.3
Yichao Zhao,Qi Li,Huihui Zhu,Cheng Jiang,Min Chen,Xiaoling Ye,Shixuan Hou,Sihao Cui,Xinmei Huang,Mengshu Cao
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease without any effective treatment. Berberine (BBR), a botanical alkaloid, possesses extensive biological activities and has significant therapeutic value in various diseases. However, the effect and potential mechanisms of BBR on pulmonary fibrosis remain elusive. In vivo, BBR was administered by gavage following intratracheal instillation of bleomycin (BLM) in a mouse model from Day 1 to Day 20. In vitro, Human Lung Fibroblast (HLF) and A549 cell lines were used to explore the effects of BBR on transforming growth factor β1 (TGF-β1) treated cells. Both cell lines were transfected with a lentivirus carrying TGF-β receptor 2 (TGFBR2) knockdown genes, and the autophagy inhibitor chloroquine (CQ) and PI3K inhibitor LY294002 were employed to investigate the underlying effects of BBR on TGF-β signaling and autophagy in pulmonary fibrosis. BBR administration attenuates pulmonary inflammation and fibrosis of BLM-induced mice in vivo. Analogously, BBR treatment significantly alleviates matrix collagen deposition and reduces the expression of fibrotic markers in TGF-β1-treated human lung fibroblasts (HLF) and alveolar epithelial cell (A549) in vitro. Mechanistically, we found that BBR downregulates the expression of TGFBR2 and suppresses TGF-β/Smad2/3 signaling in vivo and in vitro. Furthermore, BBR inhibits the activation of the PI3K/AKT/mTOR pathway and autophagy, then downregulates the expression of pro-fibrotic genes. The effect of BBR on pulmonary fibrosis was further verified using both TGF-β1-treated HLF and A549 cells with the addition of the inhibitors of PI3K, LY294002, and autophagy, CQ in vitro, respectively. Our study suggests that BBR can inhibit pulmonary fibrosis by down-regulating the expression of TGFBR2, attenuating TGF-β/Smad2/3 signal, and activating autophagy through phosphorylation of PI3K/AKT/mTOR.
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DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-11
·
IF 7
Yang Liu,Du Xing,Wang Siqi,Lin Chenggang,Li Qiqi,Li Qifa
Follicular atresia triggered by granulosa cell (GC) apoptosis severely reduces female fertility and accelerates reproductive aging. GC apoptosis is a complex process regulated by multiple factors, regulatory axes, and signaling pathways. Here, we report a novel, small regulatory network involved in GC apoptosis and follicular atresia. miR-187, a miRNA down-regulated during follicular atresia in sows, maintains TGFBR2 mRNA stability in sow GCs by directly binding to its 5’-UTR. miR-187 activates the transforming growth factor-β (TGF-β) signaling pathway and suppresses GC apoptosis via TGFBR2 activation. NORHA, a pro-apoptotic lncRNA expressed in sow GCs, inhibits TGFBR2-mediated activation of the TGF-β signaling pathway by sponging miR-187. In contrast, NORFA, a functional lncRNA associated with sow follicular atresia and GC apoptosis, enhances miR-187 and TGFBR2 expression by inhibiting NORHA and activating NFIX. Our findings define a simple regulatory network that controls GC apoptosis and follicular atresia, providing new insights into the mechanisms of GC apoptosis, follicular atresia, and female fertility.
研究领域:
生殖生物学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
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