Clinical science最新文献

Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema. 评估高海拔肺水肿中细胞游离 DNA 释放异常的细胞死亡标志物。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-20 DOI: 10.1042/CS20242052

Manzoor Ali, Krishna G Kumar, Kanika Singh, Stanzen Rabyang, Tashi Thinlas, Aastha Mishra

{"title":"Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema.","authors":"Manzoor Ali, Krishna G Kumar, Kanika Singh, Stanzen Rabyang, Tashi Thinlas, Aastha Mishra","doi":"10.1042/CS20242052","DOIUrl":"10.1042/CS20242052","url":null,"abstract":"The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier study observed altered cfDNA fragment patterns in HAPE patients and the significant correlation of these patterns with peripheral oxygen saturation levels. However, the unclear release mechanisms of cfDNA in circulation limit its characterization and clinical utility. The present study not only observed a significant increase in cfDNA levels in HAPE patients (27.03 ± 1.37 ng/ml; n = 145) compared to healthy HA sojourners (controls, 14.57 ± 0.74 ng/ml; n = 65) and highlanders (HLs, 15.50 ± 0.8 ng/ml; n = 34) but also assayed the known cell death markers involved in cfDNA release at HA. The study found significantly elevated levels of the apoptotic marker, annexin A5, and secondary necrosis or late apoptotic marker, high mobility group box 1, in HAPE patients. In addition, we observed a higher oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine, in HAPE compared with controls, suggestive of the role of oxidative DNA status in promoting the inflammatory potential of cfDNA fragments and their plausible role in manifesting HAPE pathophysiology. Extensive in vitro future assays can confirm the immunogenic role of cfDNA fragments that may act as a danger-associated molecular pattern and associate with markers of cellular stresses in HAPE.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1467-1480"},"PeriodicalIF":6.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Piezo Channels in JG cells do not Regulate Renin Expression or Renin Release to the Circulation. JG 细胞中的压电通道不会调节肾素的表达或肾素向血液循环的释放。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-20 DOI: 10.1042/CS20242089

Vidya K Nagalakshmi, Jason P Smith, Daisuke Matsuoka, Roberto Ariel Gomez, Maria Luisa Soledad Sequeira-Lopez

{"title":"Piezo Channels in JG cells do not Regulate Renin Expression or Renin Release to the Circulation.","authors":"Vidya K Nagalakshmi, Jason P Smith, Daisuke Matsuoka, Roberto Ariel Gomez, Maria Luisa Soledad Sequeira-Lopez","doi":"10.1042/CS20242089","DOIUrl":"https://doi.org/10.1042/CS20242089","url":null,"abstract":"Renin-expressing juxtaglomerular (JG) cells possess an intrinsic pressure-sensing mechanism(s) that regulates renin synthesis and release in response to changes in perfusion pressure. Although we recently described the structure of the nuclear mechanotransducer that controls renin transcription, the acute pressure-sensing mechanism that controls the rapid release of renin has not been identified. In JG cells there is an inverse relationship between intracellular calcium and renin release, the \"calcium paradox\". Since the discovery of Piezo2 as the \"touch\" receptors, there has been a significant interest in exploring whether they are also involved in other tissues beyond the skin. Given that Piezo receptors are permeable to calcium upon mechanical stimuli, it would be reasonable to hypothesize that Piezo2 controls renin synthesis and/or release in JG cells. To test this hypothesis, we used a variety of novel mouse models and JG cell-specific techniques to define whether Piezo2 controls renin expression and/or release in JG cells. Our in vivo data using constitutive and inducible Cre driver mouse lines and a variety of novel experimental approaches indicate that Piezo2 channels are not necessary for renin synthesis or release in JG cells during normal conditions or when homeostasis is threatened by hypotension, sodium depletion, or inverse changes in blood pressure. Furthermore, Piezo1 channels do not compensate for the lack of Piezo2 in JG cells. Efforts should be devoted to identifying the acute mechanosensory mechanisms controlling renin release.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in β cells. 正常妊娠和妊娠糖尿病胎盘细胞外小泡可增加β细胞中胰岛素基因的转录和含量。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-20 DOI: 10.1042/CS20241782

Faheem Seedat, Neva Kandzija, Michael J Ellis, Shuhan Jiang, Asselzhan Sarbalina, James Bancroft, Edward Drydale, Svenja S Hester, Roman Fischer, Alisha N Wade, M Irina Stefana, John A Todd, Manu Vatish

{"title":"Placental small extracellular vesicles from normal pregnancy and gestational diabetes increase insulin gene transcription and content in β cells.","authors":"Faheem Seedat, Neva Kandzija, Michael J Ellis, Shuhan Jiang, Asselzhan Sarbalina, James Bancroft, Edward Drydale, Svenja S Hester, Roman Fischer, Alisha N Wade, M Irina Stefana, John A Todd, Manu Vatish","doi":"10.1042/CS20241782","DOIUrl":"10.1042/CS20241782","url":null,"abstract":"Insulin secretion increases progressively during pregnancy to maintain normal maternal blood glucose levels. The placenta plays a crucial role in this process by releasing hormones and extracellular vesicles into the maternal circulation, which drive significant changes in pregnancy physiology. Placental extracellular vesicles, which are detectable in the plasma of pregnant women, have been shown to signal peripheral tissues and contribute to pregnancy-related conditions. While studies using murine models have demonstrated that extracellular vesicles can modulate insulin secretion in pancreatic islets, it remains unclear whether these effects translate to human biology. Understanding how placental signals enhance insulin synthesis and secretion from β cells could be pivotal in developing new therapies for diabetes. In our study, we isolated placental small extracellular vesicles from human placentae and utilised the human β cell line, EndoC-βH3, to investigate their effects on β-cell function in vitro. Our results indicate that human β cells internalise placental small extracellular vesicles, leading to enhanced insulin gene expression and increased insulin content within the β cells. Moreover, these vesicles up-regulated the expression of Annexin A1, a protein known to increase insulin content. This up-regulation of Annexin A1 holds promise as a potential mechanism by which placental small extracellular vesicles enhance insulin biosynthesis.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1481-1502"},"PeriodicalIF":6.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Relaxin improves multiple markers of wound healing and ameliorates the disturbed healing pattern of genetically diabetic mice. 撤回：松弛素能改善伤口愈合的多种指标，并改善遗传性糖尿病小鼠紊乱的愈合模式。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-20 DOI: 10.1042/CS-2013-0105_RET

引用次数: 0

Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumouroids. 内皮素-1 受体阻断剂会损害工程三维高分化浆液性卵巢癌瘤体的侵袭模式。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-20 DOI: 10.1042/CS20240371

Judith Pape, Umber Cheema, Piera Tocci, Rosanna Sestito, Ilenia Masi, Marilena Loizidou, Anna Bagnato, Laura Rosanò

{"title":"Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumouroids.","authors":"Judith Pape, Umber Cheema, Piera Tocci, Rosanna Sestito, Ilenia Masi, Marilena Loizidou, Anna Bagnato, Laura Rosanò","doi":"10.1042/CS20240371","DOIUrl":"10.1042/CS20240371","url":null,"abstract":"High-grade serous ovarian cancer (HG-SOC), accounting for 70-80% of ovarian cancer deaths, is characterized by a widespread and rapid metastatic nature, influenced by diverse cell types, cell-cell interactions, and acellular components of the tumour microenvironment (TME). Within this tumour type, autocrine and paracrine activation of the endothelin-1 receptors (ET-1R), expressed in tumour cells and stromal elements, drives metastatic progression. The lack of three-dimensional models that faithfully recapitulate the unique HG-SOC TME has been the bottleneck in performing drug screening for personalized medicine. Herein, we developed HG-SOC tumouroids by engineering a dense central artificial cancer mass (ACM) containing HG-SOC cells, nested within a compressed hydrogel recapitulating the stromal compartment comprising type I collagen, laminin, fibronectin, and stromal cells (fibroblasts and endothelial cells). ET-1-stimulated HG-SOC cells in the tumouroids showed an altered migration pattern and formed cellular aggregates, mimicking micrometastases that invaded the stroma. Compared with control cells, ET-1-stimulated tumouroids showed a higher number of invasive bodies, which were reduced by treatment with the dual ET-1 receptor (ET-1R) antagonist macitentan. In addition, ET-1 increased the size of the invading aggregates compared with control cells. This study establishes an experimental 3D multicellular model eligible for mechanical research, investigating the impact of matrix stiffness and TME interactions, which will aid drug screening to guide therapeutic decisions in HG-SOC patients.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1441-1450"},"PeriodicalIF":6.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective Effect of Mesenchymal Stromal Cells in Diabetic Nephropathy: The In vitro and In vivo Role of the M-Sec-Tunneling Nanotubes. 间充质基质细胞对糖尿病肾病的保护作用：M-Sec-隧道纳米管在体外和体内的作用

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-13 DOI: 10.1042/CS20242064

Federica Barutta, Beatrice Corbetta, Stefania Bellini, Roberto Gambino, Stefania Bruno, Shunsuke Kimura, Koji Hase, Hiroshi Ohno, Gabriella Gruden

{"title":"Protective Effect of Mesenchymal Stromal Cells in Diabetic Nephropathy: The In vitro and In vivo Role of the M-Sec-Tunneling Nanotubes.","authors":"Federica Barutta, Beatrice Corbetta, Stefania Bellini, Roberto Gambino, Stefania Bruno, Shunsuke Kimura, Koji Hase, Hiroshi Ohno, Gabriella Gruden","doi":"10.1042/CS20242064","DOIUrl":"https://doi.org/10.1042/CS20242064","url":null,"abstract":" Mitochondrial dysfunction plays an important role in the development of podocyte injury in diabetic nephropathy (DN). Tunnelling nanotubes (TNTs) are long channels that connect cells and allow organelle exchange. Mesenchymal stromal cells (MSCs) can transfer mitochondria to other cells through the M-Sec-TNTs system. However, it remains unexplored whether MSCs can form heterotypic TNTs with podocytes, thereby enabling the replacement of diabetes-damaged mitochondria. In this study, we analysed TNT formation, mitochondrial transfer, and markers of cell injury in podocytes that were pre-exposed to diabetes-related insults and then co-cultured with diabetic or non-diabetic MSCs. Furthermore, to assess the in vivo relevance, we treated DN mice with exogenous MSCs, either expressing or lacking M-Sec, carrying fluorescent-tagged mitochondria. MSCs formed heterotypic TNTs with podocytes, allowing mitochondrial transfer, via a M-Sec-dependent mechanism. This ameliorated mitochondrial function, nephrin expression, and reduced apoptosis in recipient podocytes. However, MSCs isolated from diabetic mice failed to confer cytoprotection due to Miro-1 downregulation. In experimental DN, treatment with exogenous MSCs significantly improved DN, but no benefit was observed in mice treated with MSCs lacking M-Sec. Mitochondrial transfer from exogenous MSCs to podocytes occurred in vivo in a M-Sec-dependent manner. These findings demonstrate that the M-Sec-TNT-mediated transfer of mitochondria from healthy MSCs to diabetes-injured podocytes can ameliorate podocyte damage. Moreover, M-Sec expression in exogenous MSCs is essential for providing renoprotection in vivo in experimental DN.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced Vasoconstriction in Sickle Cell Disease is Dependent on ETA Receptor Activation. 镰状细胞病的血管收缩增强依赖于 ETA 受体的激活

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-11 DOI: 10.1042/CS20240625

John Miller Allan, Brandon M Fox, Malgorzata Kasztan, Gillian C Kelly, Patrick A Molina, McKenzi A King, Jackson Colson, Leigh Wells, Latanya Bowman, Marsha Blackburn, Abdullah Kutlar, Ryan A Harris, David M Pollock, Jennifer Pollock

{"title":"Enhanced Vasoconstriction in Sickle Cell Disease is Dependent on ETA Receptor Activation.","authors":"John Miller Allan, Brandon M Fox, Malgorzata Kasztan, Gillian C Kelly, Patrick A Molina, McKenzi A King, Jackson Colson, Leigh Wells, Latanya Bowman, Marsha Blackburn, Abdullah Kutlar, Ryan A Harris, David M Pollock, Jennifer Pollock","doi":"10.1042/CS20240625","DOIUrl":"https://doi.org/10.1042/CS20240625","url":null,"abstract":"Sickle Cell Disease (SCD) carries a significant risk for poor vascular health and vascular dysfunction. High levels of vascular reactive oxygen species (ROS) as well as elevated plasma endothelin-1 (ET-1), a potent vasoconstrictor with actions via the ETA receptor, are both common phenotypes in SCD. Alpha-1 adrenergic receptor activation is a major mediator of stress-induced vasoconstriction. However, the mechanism of the SCD enhanced vasoconstrictive response is unknown. We hypothesized that SCD induces enhanced alpha-1 adrenergic mediated vasoconstriction through the ET-1/ETA receptor pathway in arterial tissues. Utilizing humanized SCD (HbSS) and genetic control (HbAA) mice, alpha-1a, but not alpha-1b or alpha-1d, receptor expression was significantly greater in aortic tissue from HbSS mice compared to HbAA mice. Significantly enhanced vasoconstriction in aortic and carotid arterial segments were observed from HbSS mice compared to HbAA mice. Treatment with ambrisentan, a selective ETA receptor antagonist, and a ROS scavenger normalized the aortic vasoconstrictive response in HbSS mice. In a randomized translational study, patients with SCD were treated with placebo or ambrisentan for 3 months, with the treatment group showing an increase in the percent brachial arterial diameter. Taken together, these data suggest that the ETA receptor pathway interaction with the adrenergic receptor pathway contributes to enhanced aortic vasoconstriction in SCD. Findings indicate the potential of ETA antagonism as a therapeutic avenue for improving vascular health in SCD.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Complex regulation of tau phosphorylation by the endothelin system in brain microvascular endothelial cells (BMVECs): link to barrier function. 脑微血管内皮细胞（BMVECs）内皮素系统对 Tau 磷酸化的复杂调控：与屏障功能的联系

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-06 DOI: 10.1042/CS20240616

Eda Karakaya, Yasir Abdul, Jazlyn Edwards, Sarah Jamil, Onder Albayram, Adviye Ergul

{"title":"Complex regulation of tau phosphorylation by the endothelin system in brain microvascular endothelial cells (BMVECs): link to barrier function.","authors":"Eda Karakaya, Yasir Abdul, Jazlyn Edwards, Sarah Jamil, Onder Albayram, Adviye Ergul","doi":"10.1042/CS20240616","DOIUrl":"10.1042/CS20240616","url":null,"abstract":"Endothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes to cerebrovascular dysfunction. ET-1 levels in postmortem brain specimens from individuals diagnosed with Alzheimer's disease (AD) and related dementias (ADRD) were shown to be related to cerebral hypoxia and disease severity. ET-1-mediated vascular dysfunction and ensuing cognitive deficits have also been reported in experimental models of AD and ADRD. Moreover, studies also showed that ET-1 secreted from brain microvascular endothelial cells (BMVECs) can affect neurovascular unit integrity in an autocrine and paracrine manner. Vascular contributions to cognitive impairment and dementia (VCID) is a leading ADRD cause known to be free of neuronal tau pathology, a hallmark of AD. However, a recent study reported cytotoxic hyperphosphorylated tau (p-tau) accumulation, which fails to bind or stabilize microtubules in BMVECs in VCID. Thus, the study aimed to determine the impact of ET-1 on tau pathology, microtubule organization, and barrier function in BMVECs. Cells were stimulated with 1 μM ET-1 for 24 h in the presence/absence of ETA (BQ123; 20 μM) or ETB (BQ788; 20 μM) receptor antagonists. Cell lysates were assayed for an array of phosphorylation site-specific antibodies and microtubule organization/stabilization markers. ET-1 stimulation increased p-tau Thr231 but decreased p-tau Ser199, Ser262, Ser396, and Ser214 levels only in the presence of ETA or ETB antagonism. ET-1 also impaired barrier function in the presence of ETA antagonism. These novel findings suggest that (1) dysregulation of endothelial tau phosphorylation may contribute to cerebral microvascular dysfunction and (2) the ET system may be an early intervention target to prevent hyperphosphorylated tau-mediated disruption of BMVEC barrier function.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1329-1341"},"PeriodicalIF":6.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Commentary: the perspectives of harnessing the power of scattered tubular-like cells for renal repair. 评论：利用分散的肾小管样细胞的力量进行肾脏修复的前景。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-06 DOI: 10.1042/CS20241405

Adam C Jones, Oleg Palygin, Daria V Ilatovskaya

引用次数: 0

Cardiac-derived CTRP9 mediates the protection of empagliflozin against diabetes-induced male subfertility in mice. 心源性 CTRP9 在保护小鼠免受糖尿病诱导的雄性不育症影响方面起着介导作用。

IF 6.7 2区医学

Clinical science Pub Date : 2024-11-06 DOI: 10.1042/CS20241477

Yang Mu, Ling-Bo Luo, Rong Huang, Zhuo-Yu Shen, Dan Huang, Shu-Hong Zhao, Jing Yang, Zhen-Guo Ma

{"title":"Cardiac-derived CTRP9 mediates the protection of empagliflozin against diabetes-induced male subfertility in mice.","authors":"Yang Mu, Ling-Bo Luo, Rong Huang, Zhuo-Yu Shen, Dan Huang, Shu-Hong Zhao, Jing Yang, Zhen-Guo Ma","doi":"10.1042/CS20241477","DOIUrl":"10.1042/CS20241477","url":null,"abstract":"Previous studies have shown beneficial effects of empagliflozin (Empa), a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2), on diabetes and cardiovascular outcomes in patients with diabetes. However, whether Empa could ameliorate diabetes mellitus (DM)-induced male spermatogenesis dysfunction remains unclear. Our study aimed to investigate the effect of Empa in the development of DM-induced male spermatogenesis dysfunction and to reveal the molecular mechanisms. DM mice were orally treated with Empa to investigate the effects of Empa on DM-induced male mice spermatogenesis dysfunction. We employed a cardiac-specific C1q/tumor necrosis factor-related protein 9 (CTRP9)-deficient mouse model and a cardiac-specific CTRP9 overexpression mouse model to investigate its role in the protection of Empa against diabetes-induced male subfertility. We found that Empa treatment could improve DM-induced male mice subfertility. Interestingly, we discovered that cardiac-derived CTRP9 was decreased in DM mice and this decrease was prevented by Empa treatment. A CTRP9 blocking antibody or cardiac-specific depletion of CTRP9 abolished the protection of Empa on DM-induced male subfertility. Cardiac-specific CTRP9 overexpression ameliorated DM-induced male subfertility. Mechanistically, we identified that cardiac-derived CTRP9 increased steroidogenesis in mice with diabetes in a PKA-dependent manner. We also provided direct evidence that activation of AMP activated protein kinase α (AMPKα)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signalling pathway by CTRP9 was responsible for the attenuation of ferroptosis in Leydig cells. In conclusions, we supposed that Empa was a potential therapeutic agent against DM-induced male mice spermatogenesis dysfunction.","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1421-1440"},"PeriodicalIF":6.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0