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Testosterone attenuates senile cavernous fibrosis by regulating TGFβR1 and galectin-1 signaling pathways through miR-22-3p

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Abstract

Erectile dysfunction (ED) is a major health problem affecting a large proportion of the general population. Testosterone also plays a key role in sexual dysfunction. In this study, we found that testosterone can inhibit cavernous fibrosis by affecting the expression of miR-22-3p, providing a new basis for research and treatment of ED. Old and young rats were used to study the effects of testosterone on cavernous fibrosis. Hematoxylin and eosin (HE) and Masson’s staining were used to observe the cavernous tissue. A luciferase assay was used to analyze the relationship between the miR-22-3p, TGFβR1, and Galectin-1 signaling pathways. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis rates of cavernosum smooth muscle cells (CSMCs) following testosterone intervention. Immunohistochemical analysis was performed to examine the positive rate of caspase 3 and Ki67. IF was used to analyze the expression of collagen IV, MMP2, and α-SMA. The levels of GnRH, tT, LH, and F-TESTO in old rats increased after testosterone intervention. miR-22-3p inhibits the expression of TGFβR1 and Galectin-1. The protein expression of TGFβR1, Galectin-1, SMAD2, and p-SMAD2 was reduced by testosterone. The expression levels of α-SMA, collagen I, collagen IV, FN, and MMP2 in the cavernous tissues of old rats treated with testosterone were significantly reduced. The levels of caspase 3 and collagen IV decreased, and the levels of MMP2, Ki67, and α-SMA increased. Testosterone and miR-22-3p inhibit CSMC apoptosis and promote cell proliferation. Testosterone promoted the expression of miR-22-3p to interfere with the expression of the cavernous TGFβR1 and Galectin-1 signaling pathways. Testosterone can reduce cavernous fibrosis during the treatment of functional ED.

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Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (No.81973863), Traditional Chinese Medicine Scientific Research Program of Hunan Province (No.2022118), Scientific research project of Hunan Provincial Department of Education (No.22B1032) and Scientific Research Program of Hunan Provincial Health Commission (No.D202303107632).

Funding

This study was funded by National Natural Science Foundation of China (No.81973863), Traditional Chinese Medicine Scientific Research Program of Hunan Province (No.2022118), Scientific research project of Hunan Provincial Department of Education (No.22B1032) and Scientific Research Program of Hunan Provincial Health Commission (No.D202303107632).

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Authors and Affiliations

  1. Department of Rehabilitation and Healthcare, Hunan University of Medicine, No. 492, Jinxi South Road, Hecheng District, Huaihua City, Hunan Province, China

    Zongren Hu, Jisong Chen, Min Luo & Qinghu He

  2. School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China

    Zongren Hu, Neng Wang & Qinghu He

  3. The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China

    Yuanting Zhang

  4. The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Min Luo

  5. School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China

    Yinfu Xiao

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  1. Zongren Hu
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  2. Yuanting Zhang
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  3. Jisong Chen
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  4. Min Luo
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  7. Qinghu He
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Contributions

ZONGREN HU and QINGHU HE designed the whole study，as well as wrote the main manuscript text. YUANTING ZHANG analyzed the experimental data. JISONG CHEN and MIN LUO prepared figures 1-6. NENG WANG did an animal experiment. YINFU XIAO did cell experiment. All authors reviewed the manuscript.

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Correspondence to Qinghu He.

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11010_2022_4641_MOESM1_ESM.jpg

Testosterone may affect miR-22-3p by regulating AR. The expression of miR-22-3p decreased under the intervention of Bicalutamide. Supplementary file1 (JPG 213 KB)

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Hu, Z., Zhang, Y., Chen, J. et al. Testosterone attenuates senile cavernous fibrosis by regulating TGFβR1 and galectin-1 signaling pathways through miR-22-3p. Mol Cell Biochem 478, 1791–1802 (2023). https://doi.org/10.1007/s11010-022-04641-8

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