Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway
Purpose: To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus- induced erectile dysfunction (DMED). Materials and Methods: DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control...
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Korean Society for Sexual Medicine and Andrology
2025-07-01
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| Series: | The World Journal of Men's Health |
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| author | Mancheng Xia Yiming Yuan Dong Fang Xiaohui Tan Fangzhou Zhao Xinfei Li Pengchao Gao Zhuo Zhou Tiegui Nan Zhongcheng Xin Xuesong Li Ruili Guan |
| author_facet | Mancheng Xia Yiming Yuan Dong Fang Xiaohui Tan Fangzhou Zhao Xinfei Li Pengchao Gao Zhuo Zhou Tiegui Nan Zhongcheng Xin Xuesong Li Ruili Guan |
| author_sort | Mancheng Xia |
| collection | DOAJ |
| description | Purpose: To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus-
induced erectile dysfunction (DMED).
Materials and Methods: DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three
groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following
the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly
for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was
inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial
pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose
(HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting
and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins.
Results: Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the
DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater
in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments
indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and
that the TGF-β pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was
severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-β signaling, as well as the overexpression of
collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs.
Conclusions: TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from
CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile
dysfunction by inhibiting the TGF-β/SMAD pathway. |
| format | Article |
| id | doaj-art-e3955c8cc1ba4e5480636012e483e5b8 |
| institution | DOAJ |
| issn | 2287-4208 2287-4690 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj-art-e3955c8cc1ba4e5480636012e483e5b82025-08-20T03:23:46ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-07-0143358059410.5534/wjmh.240065Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD PathwayMancheng Xia0https://orcid.org/0000-0002-9209-7246Yiming Yuan1https://orcid.org/0000-0002-8312-0723Dong Fang2https://orcid.org/0000-0001-6746-6559Xiaohui Tan3https://orcid.org/0000-0003-4139-8716Fangzhou Zhao4https://orcid.org/0000-0001-8109-8916Xinfei Li5https://orcid.org/0000-0002-4201-2443Pengchao Gao6https://orcid.org/0009-0001-9650-0901Zhuo Zhou7https://orcid.org/0009-0002-1396-6085Tiegui Nan8https://orcid.org/0000-0003-1325-6382Zhongcheng Xin9https://orcid.org/0000-0002-0361-2737Xuesong Li10https://orcid.org/0000-0002-7030-0856Ruili Guan11https://orcid.org/0000-0003-0422-846XDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaMale Reproductive and Sexual Medicine, Department of Urology, the Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaPurpose: To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus- induced erectile dysfunction (DMED). Materials and Methods: DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose (HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins. Results: Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and that the TGF-β pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-β signaling, as well as the overexpression of collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs. Conclusions: TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile dysfunction by inhibiting the TGF-β/SMAD pathway.diabetes mellituserectile dysfunctionfibrosistransforming growth factor beta1 |
| spellingShingle | Mancheng Xia Yiming Yuan Dong Fang Xiaohui Tan Fangzhou Zhao Xinfei Li Pengchao Gao Zhuo Zhou Tiegui Nan Zhongcheng Xin Xuesong Li Ruili Guan Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway The World Journal of Men's Health diabetes mellitus erectile dysfunction fibrosis transforming growth factor beta1 |
| title | Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway |
| title_full | Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway |
| title_fullStr | Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway |
| title_full_unstemmed | Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway |
| title_short | Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway |
| title_sort | blocking tsp1 ameliorates diabetes mellitus induced erectile dysfunction by inhibiting the tgf β smad pathway |
| topic | diabetes mellitus erectile dysfunction fibrosis transforming growth factor beta1 |
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