Physiological Reports最新文献_第3页

Effects of defined voluntary running distances coupled with high-fat diet consumption on the skeletal muscle transcriptome of male mice. 规定的自愿跑步距离加上高脂肪饮食消耗对雄性小鼠骨骼肌转录组的影响。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70170

Afrina Brishti, Sarah J Johnson, Daniel G Palmer, Md Obayed Raihan, Lin Yan, Shanon L Casperson

{"title":"Effects of defined voluntary running distances coupled with high-fat diet consumption on the skeletal muscle transcriptome of male mice.","authors":"Afrina Brishti, Sarah J Johnson, Daniel G Palmer, Md Obayed Raihan, Lin Yan, Shanon L Casperson","doi":"10.14814/phy2.70170","DOIUrl":"10.14814/phy2.70170","url":null,"abstract":"Exercise counters many adverse health effects of consuming a high-fat diet (HFD). However, complex molecular changes that occur in skeletal muscle in response to exercising while consuming a HFD are not yet known. We investigated the interplay between diverse exercise regimes and HFD consumption on the adaptation of skeletal muscle transcriptome. C57BL/6 male mice were randomized into five groups-one sedentary control group and four exercise groups. The exercise groups consisted of an unrestricted running group (8.3 km/day) and three groups that were restricted to 75%, 50%, or 25% of unrestricted running (6.3, 4.2, and 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius muscle for transcriptome analyses. DEG counts were 1347, 1823, 1103, and 1107 and there were 107, 169, 67, and 89 unique genes present in the HFD-25%, HFD-50%, HFD-75%, and HFD-U, respectively. Comparing exercise groups, we found that exercising at 50% resulted in the most differentially expressed transcripts with the MAPK and PPAR signaling pathways enriched in down- and up-regulated genes, respectively. These results demonstrate that running distance impacts the adaptation of the skeletal muscle transcriptome to exercise and suggest that middle-distance running may provide the greatest protection against high-fat diet-induced stress coupled with exercise.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 2","pages":"e70170"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009856","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

Effects of acetazolamide on intracranial pressure and brain tissue oxygenation on patients with acute brain injury: A pilot physiological study. 乙酰唑胺对急性脑损伤患者颅内压和脑组织氧合影响的初步生理研究。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70159

Anas Hachlouf, Claudia Stella, Irene Cavalli, Elisa Gouvêa Bogossian, Sophie Schuind, Marco Anderloni, Fabio Silvio Taccone

{"title":"Effects of acetazolamide on intracranial pressure and brain tissue oxygenation on patients with acute brain injury: A pilot physiological study.","authors":"Anas Hachlouf, Claudia Stella, Irene Cavalli, Elisa Gouvêa Bogossian, Sophie Schuind, Marco Anderloni, Fabio Silvio Taccone","doi":"10.14814/phy2.70159","DOIUrl":"https://doi.org/10.14814/phy2.70159","url":null,"abstract":"The effect of acetazolamide on regional brain tissue oxygenation in patients with acute brain injury (ABI) is unknown. We studied adult patients with ABI who received acetazolamide as per the treating physician's decision and had ICP and brain oxygen pressure (PbtO2) monitoring. Baseline measurements of ICP, cerebral perfusion pressure (CPP), and PbtO2 were taken before administering acetazolamide; subsequent measurements were recorded every 5 min for a total of 20 min. Mean cerebral blood velocities (FVm) and pulsatility index (PI) were measured using transcranial color-coded duplex (TCCD) sonography at baseline and after 20 min. Fourteen patients with subarachnoid hemorrhage (n = 6), traumatic brain injury (n = 7), and intracranial hemorrhage (n = 1) were included. Following administration of acetazolamide, ICP showed a significant increase within 20 min (p < 0.001), with no significant change in CPP (p = 0.08). PbtO2 demonstrated a significant increase (p < 0.001), with a noticeable change observed at 10 min after acetazolamide administration (15 [14-17] vs. 28 [26-30] mmHg). Additionally, FVm exhibited a significant increase (p < 0.001), and PI showed a reduction (p < 0.001). Administration of acetazolamide in ABI patients resulted in a significant increase in brain oxygenation, associated with a rise in ICP and FVm, suggesting increased cerebral volume and vasodilation.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 1","pages":"e70159"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953193","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

Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature. 内源性因子对热色氨酸的调节及其在核心体温下的生理功能。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70164

Makiko Kashio

引用次数: 0

Social isolation increases impulsive choice with minor changes on metabolic function in middle-aged rats. 社会隔离增加了中年大鼠的冲动选择，但代谢功能发生了微小变化。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70184

Jassmyn J Venegas, Jacob M Weisz, Chan Young Choi, Ren E Herringshaw, Omar A Nabelsi, Nu-Chu Liang

{"title":"Social isolation increases impulsive choice with minor changes on metabolic function in middle-aged rats.","authors":"Jassmyn J Venegas, Jacob M Weisz, Chan Young Choi, Ren E Herringshaw, Omar A Nabelsi, Nu-Chu Liang","doi":"10.14814/phy2.70184","DOIUrl":"10.14814/phy2.70184","url":null,"abstract":"The effects of social isolation (SI) during middle age remain unclear, so we tested the hypothesis that SI would lead to an increase in impulsive choice (IC), anxiety-like behavior, and metabolic dysfunction in middle-aged rats. Male and female rats were housed individually or in groups of four with same-sex housing mates at 11 months of age. Two months later, IC behavior was assessed using a delay-discounting task and anxiety-like behavior through a novelty-suppressed feeding (NSF) task. Lastly, glucose tolerance and insulin sensitivity following exposure to a high-fat diet were assessed using an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). The results showed that socially isolated rats displayed more IC behavior than did group-housed rats of both sexes. However, no significant effect of housing was evident in the NSF task, OGTT, or ITT. Male rats had a higher plasma insulin concentration and insulin resistance index compared to females. Our findings demonstrate that SI in middle age is sufficient to increase IC behavior and highlight inherent sex-specific differences in metabolic profiles. These findings underscore the importance of investigating mechanisms that underlie the effects of social isolation during different stages of life.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 2","pages":"e70184"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009860","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

Interoception, cardiac health, and heart failure: The potential for artificial intelligence (AI)-driven diagnosis and treatment. 内感受、心脏健康和心力衰竭：人工智能驱动的诊断和治疗的潜力。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70146

Mahavir Singh, Anmol Babbarwal, Sathnur Pushpakumar, Suresh C Tyagi

{"title":"Interoception, cardiac health, and heart failure: The potential for artificial intelligence (AI)-driven diagnosis and treatment.","authors":"Mahavir Singh, Anmol Babbarwal, Sathnur Pushpakumar, Suresh C Tyagi","doi":"10.14814/phy2.70146","DOIUrl":"10.14814/phy2.70146","url":null,"abstract":"\"I see, I forget, I read aloud, I remember, and when I do read purposefully by writing it, I do not forget it.\" This phenomenon is known as \"interoception\" and refers to the sensing and interpretation of internal body signals, allowing the brain to communicate with various body systems. Dysfunction in interoception is associated with cardiovascular disorders. We delve into the concept of interoception and its impact on heart failure (HF) by reviewing and exploring neural mechanisms underlying interoceptive processing. Furthermore, we review the potential of artificial intelligence (AI) in diagnosis, biomarker development, and HF treatment. In the context of HF, AI algorithms can analyze and interpret complex interoceptive data, providing valuable insights for diagnosis and treatment. These algorithms can identify patterns of disease markers that can contribute to early detection and diagnosis, enabling timely intervention and improved outcomes. These biomarkers hold significant potential in improving the precision/efficacy of HF. Additionally, AI-powered technologies offer promising avenues for treatment. By leveraging patient data, AI can personalize therapeutic interventions. AI-driven technologies such as remote monitoring devices and wearable sensors enable the monitoring of patients' health. By harnessing the power of AI, we should aim to advance the diagnosis and treatment strategies for HF. This review explores the potential of AI in diagnosing, developing biomarkers, and managing HF.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 1","pages":"e70146"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953195","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

Skeletal muscle ribosome analysis: A comparison of common assay methods and utilization of a novel RiboAb antibody cocktail. 骨骼肌核糖体分析：比较常见的分析方法和利用一种新的核糖抗体鸡尾酒。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70173

Joshua S Godwin, J Max Michel, C Brooks Mobley, Gustavo A Nader, Michael D Roberts

{"title":"Skeletal muscle ribosome analysis: A comparison of common assay methods and utilization of a novel RiboAb antibody cocktail.","authors":"Joshua S Godwin, J Max Michel, C Brooks Mobley, Gustavo A Nader, Michael D Roberts","doi":"10.14814/phy2.70173","DOIUrl":"https://doi.org/10.14814/phy2.70173","url":null,"abstract":"While total RNA concentrations putatively represent ribosome content, there is a need to homologize various quantification approaches. Thus, total RNA concentrations ([RNA]) provided through UV-Vis spectroscopy (UV), fluorometry-only (Fluor), and fluorometry-based microfluidic chip electrophoresis (MFGE) were examined in C2C12 myotubes and mouse skeletal muscle to determine if values aligned with [18S + 28S rRNA] (i.e., criterion ribosome metric). A novel antibody cocktail (termed RiboAb) was also tested and compared to [18S + 28S rRNA] in these models. In myotubes, 24-h IGF-1 treatments increased [18S + 28S rRNA] (~2.0-fold) and [RNA] based on UV (~1.9-fold), Fluor (~2.3 fold), and MFGE (~2.1-fold). In C57BL/6 mice, 10 days of mechanical overload (MOV) elevated plantaris [18S + 28S rRNA] (~1.7-fold) and [RNA] according to UV (~1.5-fold), Fluor (~1.6-fold), and MFGE (~1.8-fold). Myotube and mouse plantaris RiboAb levels were significantly higher with IGF-1 treatments and MOV, respectively, versus controls (1.3-fold and 1.7-fold, respectively), and values correlated with [18S + 28S rRNA] (r = 0.637 and r = 0.853, respectively, p ≤ 0.005). UV, Fluor, and MFGE [RNA] are seemingly valid surrogates of cell/tissue ribosome content, although each method has advantages (e.g., ease of use) and disadvantages (e.g., magnitudes of bias) discussed herein. Finally, the RiboAb cocktail may also represent ribosome content, although this should be further explored in other models.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 1","pages":"e70173"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952969","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

Genetic diversity leads to differential inflammatory responses to cigarette smoke in mice.

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70199

Md Imam Faizan, Gagandeep Kaur, Sadiya Bi Shaikh, Felix Effah, Hoshang Unwalla, Irfan Rahman

{"title":"Genetic diversity leads to differential inflammatory responses to cigarette smoke in mice.","authors":"Md Imam Faizan, Gagandeep Kaur, Sadiya Bi Shaikh, Felix Effah, Hoshang Unwalla, Irfan Rahman","doi":"10.14814/phy2.70199","DOIUrl":"10.14814/phy2.70199","url":null,"abstract":"The use of genetically diverse mouse models offers a more accurate reflection of human genetic variability, improving the translatability of findings to heterogeneous human populations. This approach is particularly valuable in understanding diverse immune responses to disease by environmental exposures. This study investigates the inflammatory responses to acute exposures to mainstream cigarette smoke (CS) and environmental tobacco smoke (ETS) in two genetically diverse mouse strains, CC002/UncJ (UNC) & Diversity Outbred (J:DO). The UM-HET3 (HET3) mouse strain, typically used in aging intervention studies, has also been used to evaluate the translatability of this model for age-associated pathologies. The study involves a comprehensive approach, including BALF cytokine analysis, evaluation of lung tissue architecture, assessment of macrophages and its associated proteins (MMP9 & MMP12) abundance. Several cytokines/chemokines were found to be upregulated across three strains. Notably, the UNC strain exclusively showed upregulation of TNF-α, IL-17A, and IL-13, whereas the J:DO showed an upregulation in KC. The number of alveolar macrophages in the lungs of UNC mice was very low at baseline compared to other strains studied in this study, which is indicative of some inherent shift in the pulmonary immune profiles of these inbred mice. In contrast, the J:DO strain, characterized by genetic outbreeding, showed a much more robust lung macrophage response comparable to C57BL/6J. The findings provide valuable insight into how genetic diversity affects immune responses in response to acute CS/ETS exposure, with implications for understanding diverse human responses to environmental stressors in studying lung pathophysiology.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 2","pages":"e70199"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024527","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

Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types. 基因组分析揭示了p21活化激酶的改变与多种癌症类型的患者生存之间的负相关。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70192

Jessie M Vo, Linh M La, Ananda V Anderson, Abdulaziz H Alanazi, Payaningal R Somanath

{"title":"Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types.","authors":"Jessie M Vo, Linh M La, Ananda V Anderson, Abdulaziz H Alanazi, Payaningal R Somanath","doi":"10.14814/phy2.70192","DOIUrl":"https://doi.org/10.14814/phy2.70192","url":null,"abstract":"Cancer is a complex disease with profound societal and economic impacts, especially in metastatic cases where treatment challenges arise due to the absence of reliable biomarkers and effective therapies. While P21-activated kinases (PAKs) play a key role in cancer progression, their potential as predictive markers for metastasis and therapeutic targets has not been fully explored. We hypothesized that genetic alterations in PAK isoforms could be linked to reduced overall patient survival. To investigate this, we used data from the cBioPortal for Cancer Genomics, analyzing several randomized, multicentered phase-3 clinical trial datasets. The analysis revealed significant genetic alterations in PAK genes, particularly in cancers such as breast, prostate, pancreatic, and lung. Notably, elevated PAK expression was associated with poorer survival outcomes in prostate and breast cancer patients. In pancreatic and lung cancers, although a trend of poorer survival with PAK alterations was observed, it was not statistically significant. Our findings underscore the importance of PAK isoforms as potential biomarkers and therapeutic targets, particularly in metastatic cancers. Further research could lead to improved patient outcomes through targeted interventions aimed at PAK-related pathways, with PAK serving as a reliable biomarker for the precise diagnosis, monitoring, and personalization of treatment strategies.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 1","pages":"e70192"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932610","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

A patient choice-driven lifestyle intervention lowers HbA1c in type 2 diabetes: A feasibility study. 患者选择驱动的生活方式干预降低2型糖尿病患者的HbA1c：一项可行性研究

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70163

Nathan R Weeldreyer, Mindy L McEntee, Matthew P Martin, Chong D Lee, Farshad Fani Marvasti, Glenn A Gaesser, Rodger Kessler, Siddhartha S Angadi

{"title":"A patient choice-driven lifestyle intervention lowers HbA1c in type 2 diabetes: A feasibility study.","authors":"Nathan R Weeldreyer, Mindy L McEntee, Matthew P Martin, Chong D Lee, Farshad Fani Marvasti, Glenn A Gaesser, Rodger Kessler, Siddhartha S Angadi","doi":"10.14814/phy2.70163","DOIUrl":"10.14814/phy2.70163","url":null,"abstract":"Type 2 diabetes (T2D) is a common metabolic disorder in which only 25% of patients meet management targets. While the primary care setting is positioned to provide lifestyle management education, studies are lacking which integrate behavior interventions in this setting utilizing clinic staff. Thus, we evaluated a 90-day lifestyle intervention for management of glycemia at a family practice clinic administered by clinic medical assistants. Twenty patients with non-insulin-dependent T2D completed a 90-day intervention driven by patient choices of nutrition and physical activity. Medical assistants were trained by members of the study team and administered the intervention under nurse practitioner supervision. HbA1c trended toward significant reduction 8.59 ± 0.9% to 8.15 ± 1.2% (p = 0.051, 95% CI: -0.88 to 0.003). Modest reductions were observed for waist circumference (115.5 ± 12.6 vs. 112.5 ± 15.2 cm; p = 0.014, 95% CI: -5.66 to -0.26), body weight (97.7 ± 21.9 vs. 95.6 ± 23.9 kg; p = 0.016. 95% CI: -3.84 to -0.31), and BMI (33.7 ± 7.2 vs. 32.8 ± 7.5 kg/m2; p = 0.028, 95% CI: -1.29 to -0.12). This 90-day, patient choice-intervention was successful at lowering HbA1c in patients with T2D. Our study is limited by a lack of control group, and results should be interpreted as such. These data have implications for team-based care models in clinic settings to improve health outcomes in patients with T2D.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 2","pages":"e70163"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009855","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

Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease. 降低升高的Gli3并不改变常染色体隐性遗传性多囊肾病的进展。

IF 2.2

Physiological Reports Pub Date : 2025-01-01 DOI: 10.14814/phy2.70191

Lauren G Russell, Maria Kolatsi-Joannou, Laura Wilson, Jennifer C Chandler, Nuria Perretta Tejedor, Georgie Stagg, Karen L Price, Christopher J Rowan, Tessa Crompton, Norman D Rosenblum, Paul J D Winyard, David A Long

{"title":"Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.","authors":"Lauren G Russell, Maria Kolatsi-Joannou, Laura Wilson, Jennifer C Chandler, Nuria Perretta Tejedor, Georgie Stagg, Karen L Price, Christopher J Rowan, Tessa Crompton, Norman D Rosenblum, Paul J D Winyard, David A Long","doi":"10.14814/phy2.70191","DOIUrl":"10.14814/phy2.70191","url":null,"abstract":"Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition. In contrast, the role of the Hh pathway in ARPKD is poorly understood. We hypothesized that Hh pathway activity would be elevated during ARPKD pathogenesis, and its modulation may slow disease progression. We utilized Cpk mice which phenocopy ARPKD and generated a PKHD1-mutant spheroid model in human collecting ducts. Significantly elevated levels of the Hh transcriptional effector Gli3 were found in Cpk mice, a finding replicated in PKHD1-mutant spheroids. In Cpk mice, total GLI3 and GLI3 repressor protein levels were also increased. Reduction of increased Gli3 levels via heterozygous genetic deletion in Cpk mice did not affect cyst formation. Additionally, lowering GLI3 transcripts to wildtype levels did not influence PKHD1-mutant spheroid size. Collectively, these data suggest attenuation of elevated Gli3 does not modulate murine and human models of ARPKD.","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 2","pages":"e70191"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009859","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