Journal of Smooth Muscle Research最新文献

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Antidiarrheal and antispasmodic effects of methanol fraction of Ammodaucus leucotrichus in gastrointestinal problems: an integrative medicine approach. Ammodaucus leucotrichus甲醇部分对胃肠道问题的止泻和解痉作用:一种综合医学方法。
Journal of Smooth Muscle Research Pub Date : 2024-01-01 DOI: 10.1540/jsmr.60.39
Ahmed Karim, Sanae Malek, Mohamed Marghich, Ouafa Amrani, Abdelhay Addous, Leila Beyi, Mohammed Aziz
{"title":"Antidiarrheal and antispasmodic effects of methanol fraction of Ammodaucus leucotrichus in gastrointestinal problems: an integrative medicine approach.","authors":"Ahmed Karim, Sanae Malek, Mohamed Marghich, Ouafa Amrani, Abdelhay Addous, Leila Beyi, Mohammed Aziz","doi":"10.1540/jsmr.60.39","DOIUrl":"10.1540/jsmr.60.39","url":null,"abstract":"<p><p>Diarrhea is the second leading cause of death in children under five years of age globally. Traditional medicinal practices often use plants to manage gastrointestinal issues. Ammodaucus leucotrichus is a medicinal plant that holds significant importance in Moroccan traditional medicine for treating gastrointestinal problems. This study aimed to validate the traditional use of A. leucotrichus by providing scientific evidence for its efficacy. We evaluated the effectiveness of the methanol fraction of A. leucotrichus in alleviating diarrhea and reducing smooth muscle contractions using comprehensive in vivo and in vitro models. In vitro experiments were performed using an isotonic transducer in the jejunum of rats and rabbits. In vivo antidiarrheal effects were evaluated in mice with castor oil-induced diarrhea. The methanol fraction of A. leucotrichus (MFAl) inhibited diarrhea in a dose-dependent manner. It also exhibited spasmolytic activity at doses ranging from 5.5 to 65 μg/ml, with IC<sub>50</sub> values of 43.43 ± 2.63 μg/ml for potassium chloride (KCl) and 28.91 ± 0.43 μg/ml for carbachol (CCh). The obtained spasmolytic activities were comparable to those of a non-competitive antagonist of calcium channels and muscarinic receptors by rightward and downward shifts in the concentration-response curves for calcium and carbachol. Our results demonstrate that, with the addition of nifedipine, the spasmolytic effect of MFAl decreased by 70.11%. This indicates that the spasmolytic effect of MFAl is possibly mediated by the inhibition of Ca<sup>2+</sup> influx. In addition, the presence of hexamethonium significantly modified the relaxation effect of MFAl by 46.20%, indicating that MFAl also acts through nicotinic receptors. These findings support the traditional use of A. leucotrichus for gastrointestinal disorders and highlight the need for further research to develop new anti-diarrheal and anti-spasmodic treatments.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"60 ","pages":"39-53"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Relationship between internal diameter and vasoconstriction in human varicose veins. 人体静脉曲张内径与血管收缩之间的关系。
Journal of Smooth Muscle Research Pub Date : 2024-01-01 DOI: 10.1540/jsmr.60.31
Atsuko Yokota, Takayuki Matsumoto, Takayuki Nagano, Masachika Kuwabara, Eisaku Nakamura, Ryuichi Yamamoto, Naoko Tanaka-Totoribe
{"title":"Relationship between internal diameter and vasoconstriction in human varicose veins.","authors":"Atsuko Yokota, Takayuki Matsumoto, Takayuki Nagano, Masachika Kuwabara, Eisaku Nakamura, Ryuichi Yamamoto, Naoko Tanaka-Totoribe","doi":"10.1540/jsmr.60.31","DOIUrl":"10.1540/jsmr.60.31","url":null,"abstract":"<p><p>Varicose veins are common lower extremity venous disorders characterized by dilated veins and incompetent valves. Although maintaining the required vein wall tone for adaptive responses depends on a proper contractile function of the human saphenous smooth muscle, the contractile properties of varicose veins are mostly unknown. We investigated the relationship between contractile responses and the internal diameter of human saphenous varicose veins. The absolute contractile forces induced by potassium chloride (KCl, 60 mmol/l), serotonin (5-hydroxytryptamine [5-HT], 10 µmol/l), and noradrenaline (NAd, 10 µmol/l) were similar between normal saphenous veins (control) and varicose veins. When the contractile forces were normalized to the internal diameter in each preparation, the contractile responses to these stimuli were significantly lower in varicose veins than in the control veins. Furthermore, varicose veins were divided into three groups according to their internal diameter (group 1, 3-4.5 mm; group 2, 4.5-6 mm; group 3, >6 mm). The contractile responses induced by KCl, 5-HT, and NAd did not differ between groups 1 and 2 and the control group, while the contractile responses in group 3 were significantly lower than those in the control group. Moreover, the contractions induced by KCl and NAd in Group 3 were smaller than those in group 1 or group 2. This trend was also observed in 5-HT-induced contractions, although the results were not statistically significant. In conclusion, contractile responses in varicose veins may be altered by an increase in internal diameter, although adequate contractile responses are preserved in some diameters.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"60 ","pages":"31-38"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protocol for gene knockdown using siRNA in organotypic cultures of murine gastric muscle. 在小鼠胃肌器官型培养中使用siRNA基因敲除的方案。
Journal of Smooth Muscle Research Pub Date : 2024-01-01 DOI: 10.1540/jsmr.60.64
Negar Taheri, Egan L Choi, Yuebo Zhang, Yujiro Hayashi
{"title":"Protocol for gene knockdown using siRNA in organotypic cultures of murine gastric muscle.","authors":"Negar Taheri, Egan L Choi, Yuebo Zhang, Yujiro Hayashi","doi":"10.1540/jsmr.60.64","DOIUrl":"10.1540/jsmr.60.64","url":null,"abstract":"<p><p>Understanding the molecular interactions within the neuromuscular apparatus in the stomach is crucial for understanding their role in maintaining interstitial cells, such as the interstitial cells of Cajal (ICC), smooth muscle, and enteric neurons, as well as their contribution to gastric motility in both healthy and diseased states. Disruptions of these systems can lead to various gastric motor disorders and diseases, making it essential to explore their functions in detail. We herein present a protocol for gene knockdown using small interfering RNA (siRNAs) in organotypic culture. This ex vivo approach allows the precise manipulation of the gene expression in a tissue environment that closely mimics in vivo conditions, providing valuable insights into the gene function and its effects on gastric physiology. The protocol includes detailed steps for tissue preparation to ensure the preservation of the gastric muscles and the associated neuromuscular apparatus. We then describe the process of siRNA-mediated gene knockdown, offering tips for optimizing transfection efficiency and gene silencing. Additionally, we outline methods for analyzing the effectiveness of knockdown, including both quantitative and qualitative methods for the evaluation of the target gene expression. This protocol is adaptable to various research needs, allowing researchers to focus on specific genes of interest within the neuromuscular system of the stomach. By applying this approach, investigators can deepen their understanding of the molecular mechanisms underlying gastric motility and contribute to the development of new therapeutic strategies for treating gastric motor disorders and diseases.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"60 ","pages":"64-71"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical characteristics and manometric findings of esophageal achalasia-a systematic review regarding differences among three subtypes. 食管贲门失弛缓症的临床特征和压力测量结果——关于三种亚型差异的系统综述。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.14
Ryo Katsumata, Noriaki Manabe, Hiroyuki Sakae, Kenta Hamada, Maki Ayaki, Takahisa Murao, Minoru Fujita, Tomoari Kamada, Hirofumi Kawamoto, Ken Haruma
{"title":"Clinical characteristics and manometric findings of esophageal achalasia-a systematic review regarding differences among three subtypes.","authors":"Ryo Katsumata,&nbsp;Noriaki Manabe,&nbsp;Hiroyuki Sakae,&nbsp;Kenta Hamada,&nbsp;Maki Ayaki,&nbsp;Takahisa Murao,&nbsp;Minoru Fujita,&nbsp;Tomoari Kamada,&nbsp;Hirofumi Kawamoto,&nbsp;Ken Haruma","doi":"10.1540/jsmr.59.14","DOIUrl":"https://doi.org/10.1540/jsmr.59.14","url":null,"abstract":"<p><p>Esophageal achalasia is classified into three subtypes according to manometric findings. Since several factors, including clinical characteristics and treatment response, have been reported to differ among the subtypes, the underlying pathogenesis may also differ. However, a comprehensive understanding regarding the differences is still lacking. We therefore performed a systematic review of the differences among the three subtypes of achalasia to clarify the current level of comprehension. In terms of clinical features, type III, which is the least frequently diagnosed of the three subtypes, showed the oldest age and most severe symptoms, such as chest pain. In contrast, type I showed a higher prevalence of lung complications, and type II showed weight loss more frequently than the other types. Histopathologically, type I showed a high loss of ganglion cells in esophagus, and on a molecular basis, type III had elevated serum pro-inflammatory cytokine levels. In addition to peristalsis and the lower esophageal sphincter (LES) function, the upper esophageal sphincter (UES) function of achalasia has attracted attention, as an impaired UES function is associated with severe aspiration pneumonia, a fatal complication of achalasia. Previous studies have indicated that type II shows a higher UES pressure than the other subtypes, while an earlier decline in the UES function has been confirmed in type I. Differences in the treatment response are also crucial for managing achalasia patients. A number of studies have reported better responses in type II cases and less favorable responses in type III cases to pneumatic dilatation. These differences help shed light on the pathogenesis of achalasia and support its clinical management according to the subtype.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"14-27"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/5d/jsmr-59-014.PMC10036217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Garcinia buchananii stem bark extract and its bioactive constituents manniflavanone, GB-2 and buchananiflavanone attenuate intestinal inhibitory neuromuscular transmission. 黄芩茎皮提取物及其生物活性成分甘露黄酮、GB-2和黄芩黄酮可减弱肠道抑制性神经肌肉传递。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.34
Savannah Patterson, Michael Elder Waters, Nancy Braman, Roan Willson, Rodney A Hill, Jakob Magolan, Thomas Hofmann, Timo D Stark, Onesmo B Balemba
{"title":"Garcinia buchananii stem bark extract and its bioactive constituents manniflavanone, GB-2 and buchananiflavanone attenuate intestinal inhibitory neuromuscular transmission.","authors":"Savannah Patterson,&nbsp;Michael Elder Waters,&nbsp;Nancy Braman,&nbsp;Roan Willson,&nbsp;Rodney A Hill,&nbsp;Jakob Magolan,&nbsp;Thomas Hofmann,&nbsp;Timo D Stark,&nbsp;Onesmo B Balemba","doi":"10.1540/jsmr.59.34","DOIUrl":"https://doi.org/10.1540/jsmr.59.34","url":null,"abstract":"<p><p>Garcinia buchananii stem bark extract (GBB), commonly used for treating diarrhea in Africa, triggers ectopic aboral contractions, causing inhibition of propulsive motility in the colon ex vivo. To determine whether or not these effects were associated with decreased inhibitory neuromuscular transmission, the responsible constituent compounds, and mechanisms of action, we studied the effects of GBB and specific fractions and flavanones isolated from GBB on intestinal motility using pellet propulsion assays in guinea pig distal colons. In addition, microelectrode recordings were used to measure the effects on the inhibitory junction potentials (IJPs) in the porcine ileum and descending colon smooth muscle. Psychoactive Drug Screening Program secondary receptor functional assays were used to determine whether or not GBB and its constituent compounds act via purinergic (P2Y) and muscarinic receptors. GBB inhibited propulsive motility, but (2R,3S,2″R,3″R)-manniflavanone (MNF), (2R,3S,2″R,3″R)-GB-2 (GB-2) and (2R,3S,2″S)-buchananiflavanone (BNF), the main ingredients of GBB, did not affect motility. We discovered that, in the porcine descending colon, IJPs contained purinergic, nitrergic, and nonpurinergic nonnitrergic components. Furthermore, ileal IJPs were purely purinergic. GBB blocked all components of IJPs, while MNF and GB-2 inhibited purinergic IJPs only. BNF inhibited the purinergic and nonpurinergic components of IJPs. MRS2365, a Y1 (P2Y) agonist, did not evoke sustained membrane hyperpolarization in the presence of GBB. However, GBB, MNF, GB-2 and BNF did not affect P2Y or muscarinic receptors. In conclusion, inhibitory neuromuscular transmission in the porcine descending colon involves all components of IJPs. GBB decreases inhibitory neuromuscular transmission, likely by the actions of MNF, GB-2 and BNF. These effects do not involve P2Y or muscarinic receptors.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"34-57"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/48/jsmr-59-034.PMC10323250.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach. 再次检查以血管平滑肌为中心的方法治疗肌营养不良。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.67
Senthilkumar Preethy, Naoki Yamamoto, Shiro Osaza, Kadalraja Raghavan, Vidyasagar Devaprasad Dedeepiya, Masaru Iwasaki, Samuel Jk Abraham
{"title":"Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach.","authors":"Senthilkumar Preethy, Naoki Yamamoto, Shiro Osaza, Kadalraja Raghavan, Vidyasagar Devaprasad Dedeepiya, Masaru Iwasaki, Samuel Jk Abraham","doi":"10.1540/jsmr.59.67","DOIUrl":"10.1540/jsmr.59.67","url":null,"abstract":"<p><p>In contrast to the long-standing focus on the pathophysiology of skeletal muscles in the hunt for a cure for Duchenne muscular dystrophy (DMD), we opine that the malfunctioning of dystrophin produced by vascular smooth muscle is a major contributor to the pathology of the illness. We believe that a biological response modifier glucan (BRMG), which has been shown in clinical studies of DMD to boost the expression of vascular smooth muscle dystrophin and provide anti-fibrotic and anti-inflammatory effects, may play a key role in reducing the pathogenesis of DMD. According to the evaluation of biomarkers, this BRMG, which is safe and side-effect-free, reduces the pathogenesis of DMD. We describe the possible mechanisms of action by which this BRMG helps in alleviating the symptoms of DMD by targeting smooth muscle dystrophin, in addition to its advantages over other therapeutic modalities, as well as how it can serve as a valuable adjunct to existing therapies. We suggest that using BRMG adjuncts that target smooth muscle dystrophin would be a potential therapeutic approach that prolongs the lifespan and extends the duration of ambulation from the onset of DMD. Further studies are needed to validate this hypothesis.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"67-80"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/f9/jsmr-59-067.PMC10482562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interstitial cells of Cajal in gastrointestinal inflammatory diseases. 胃肠道炎性疾病中的Cajal间质细胞。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.1
Noriyuki Kaji, Masatoshi Hori
{"title":"Interstitial cells of Cajal in gastrointestinal inflammatory diseases.","authors":"Noriyuki Kaji,&nbsp;Masatoshi Hori","doi":"10.1540/jsmr.59.1","DOIUrl":"https://doi.org/10.1540/jsmr.59.1","url":null,"abstract":"<p><p>The gastrointestinal (GI) tract is a vital organ that digests food, absorbs nutrients, and excretes waste. Normal GI motility is the basis for these functions. The interstitial cells of Cajal (ICC) in the GI muscularis layer promote GI motility together with the enteric nervous system and smooth muscle cells. Since GI motility results from complex coordination of these heterogeneous cells, failure of any one of them can lead to GI dysmotility. Knowledge about ICC in physiological conditions has accumulated in recent decades, while the pathophysiology of ICC in GI inflammatory diseases, such as inflammatory bowel disease, is not well understood. In this review, we summarize the previous studies about the pathophysiological changes of ICC in inflammatory diseases and discuss the inflammatory mediators that induce ICC dysfunction.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/50/6e/jsmr-59-001.PMC9926098.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10777836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct active Fyn-paxillin interaction regulates vascular smooth muscle cell migration. 直接活性Fyn-paxillin相互作用调节血管平滑肌细胞迁移。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.58
Ying Zhang, Hiroko Kishi, Sei Kobayashi
{"title":"Direct active Fyn-paxillin interaction regulates vascular smooth muscle cell migration.","authors":"Ying Zhang,&nbsp;Hiroko Kishi,&nbsp;Sei Kobayashi","doi":"10.1540/jsmr.59.58","DOIUrl":"https://doi.org/10.1540/jsmr.59.58","url":null,"abstract":"<p><p>Vascular smooth muscle cell (VSMC) migration plays an important role in cardiovascular diseases, including atherosclerotic plaque formation and restenosis after vascular intervention. The mechanisms involved in VSMC migration are complex and have not been fully elucidated. Recently, we discovered a novel interaction, direct binding of active Fyn-paxillin at focal adhesions, which plays an important role in actin stress fiber formation and migration in VSMCs. In this review, we highlight paxillin as an intermediate signaling molecule that mediates actin stress fiber formation and VSMC migration through the Fyn/paxillin/Rho-kinase signaling pathway by directly binding to active Fyn. We also discuss the inhibition of VSMC migration by blocking the active Fyn-paxillin interaction and the potential of this interaction as a therapeutic target for cardiovascular diseases.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"58-66"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Sex differences in the central regulation of colorectal motility in response to noxious stimuli. 有害刺激下结肠直肠运动中枢调节的性别差异。
Journal of Smooth Muscle Research Pub Date : 2023-01-01 DOI: 10.1540/jsmr.59.28
Kazuhiro Horii, Tomoya Sawamura, Natsufu Yuki, Takahiko Shiina, Yasutake Shimizu
{"title":"Sex differences in the central regulation of colorectal motility in response to noxious stimuli.","authors":"Kazuhiro Horii,&nbsp;Tomoya Sawamura,&nbsp;Natsufu Yuki,&nbsp;Takahiko Shiina,&nbsp;Yasutake Shimizu","doi":"10.1540/jsmr.59.28","DOIUrl":"https://doi.org/10.1540/jsmr.59.28","url":null,"abstract":"<p><p>Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous system. Noxious stimuli in the colorectum of anesthetized male rats enhance colorectal motility by activating monoaminergic neurons in descending pain inhibitory pathways from the brainstem to the lumbosacral spinal cord. These monoaminergic neurons release serotonin and dopamine into the lumbosacral spinal cord, resulting in the increment of colorectal motility. In female rats, in contrast, noxious stimuli in the colorectum have no effect on colorectal motility. We clarified that GABAergic inhibition in the lumbosacral spinal cord masks the enhancement of colorectal motility induced by monoamines in female animals. Considering that IBS patients often show visceral hypersensitivity and hyperalgesia, our studies suggest that differences in the descending neurons that respond to painful stimuli are involved in various sex differences in abnormal bowel habits.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"59 ","pages":"28-33"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/cf/jsmr-59-028.PMC10131095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10069032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucose-6-phosphate dehydrogenase and MEG3 controls hypoxia-induced expression of serum response factor (SRF) and SRF-dependent genes in pulmonary smooth muscle cell 葡萄糖-6-磷酸脱氢酶和MEG3控制缺氧诱导的肺平滑肌细胞血清反应因子(SRF)及其依赖基因的表达
Journal of Smooth Muscle Research Pub Date : 2022-04-29 DOI: 10.1540/jsmr.58.34
Atsushi Kitagawa, C. Jacob, S. Gupte
{"title":"Glucose-6-phosphate dehydrogenase and MEG3 controls hypoxia-induced expression of serum response factor (SRF) and SRF-dependent genes in pulmonary smooth muscle cell","authors":"Atsushi Kitagawa, C. Jacob, S. Gupte","doi":"10.1540/jsmr.58.34","DOIUrl":"https://doi.org/10.1540/jsmr.58.34","url":null,"abstract":"Although hypoxia induces aberrant gene expression and dedifferentiation of smooth muscle cells (SMCs), mechanisms that alter dedifferentiation gene expression by hypoxia remain unclear. Therefore, we aimed to gain insight into the hypoxia-controlled gene expression in SMCs. We conducted studies using SMCs cultured in 3% oxygen (hypoxia) and the lungs of mice exposed to 10% oxygen (hypoxia). Our results suggest hypoxia upregulated expression of transcription factor CP2-like protein1, krüppel-like factor 4, and E2f transcription factor 1 enriched genes including basonuclin 2 (Bcn2), serum response factor (Srf), polycomb 3 (Cbx8), homeobox D9 (Hoxd9), lysine demethylase 1A (Kdm1a), etc. Additionally, we found that silencing glucose-6-phosphate dehydrogenase (G6PD) expression and inhibiting G6PD activity downregulated Srf transcript and hypomethylation of SMC genes (Myocd, Myh11, and Cnn1) and concomitantly increased their expression in the lungs of hypoxic mice. Furthermore, G6PD inhibition hypomethylated MEG3, a long non-coding RNA, gene and upregulated MEG3 expression in the lungs of hypoxic mice and in hypoxic SMCs. Silencing MEG3 expression in SMC mitigated the hypoxia-induced transcription of SRF. These findings collectively demonstrate that MEG3 and G6PD codependently regulate Srf expression in hypoxic SMCs. Moreover, G6PD inhibition upregulated SRF-MYOCD-driven gene expression, determinant of a differentiated SMC phenotype.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"58 1","pages":"34 - 49"},"PeriodicalIF":0.0,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43880956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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