Article
Biochemistry & Molecular Biology
Theodoros Eleftheriadis, Georgios Pissas, Spyridon Golfinopoulos, Maria Efthymiadi, Christina Poulianiti, Maria Anna Polyzou Konsta, Vassilios Liakopoulos, Ioannis Stefanidis
Summary: This study evaluated the response of renal proximal tubular epithelial cells (RPTECs) to high albumin concentration, focusing on the unfolded protein response (UPR) and DNA damage response (DDR). The results showed that albumin led to reactive oxygen species (ROS) overproduction and protein modification, which activated both UPR and DDR. This resulted in cellular apoptosis, senescence, and epithelial-to-mesenchymal transition (EMT). While agents against endoplasmic reticulum stress (ERS) only partially alleviated the harmful effects, inhibiting ROS upregulation prevented both UPR and DDR. Therefore, suppressing ROS overproduction may be more effective in mitigating the deleterious effects of albumin overload.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hua Fu, Yong-Hong Gu, Juan Tan, Ye-Ning Yang, Guo-Hui Wang
Summary: The crosstalk between macrophages and tubular epithelial cells is important in the progression of renal fibrosis. In this study, the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of tubular epithelial cells, and the development of renal fibrosis was revealed. circACTR2 promoted the activation of NLRP3 inflammasome, inflammation in macrophages, and stimulated EMT and fibrosis of tubular epithelial cells by sponging miR-561. Knocking down circACTR2 and overexpressing miR-561 may benefit the treatment of renal fibrosis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Urology & Nephrology
Linlin Li, Hong Ye, Qiaoling Chen, Lixin Wei
Summary: This study investigated the function of COL28 in renal tubular cells by examining its mRNA expression and the effects of its overexpression on human tubular cells. The results showed that COL28 was expressed at low levels in normal renal tissues and higher levels in fibrotic kidney disease. Overexpression of COL28 promoted cell proliferation and migration and may be involved in epithelial-to-mesenchymal transition (EMT). COL28 could be a potential therapeutic target for renal fibrotic diseases.
Article
Pharmacology & Pharmacy
Zhiwen Xie, Yongqing Zhang, Wenlan Sun, Shan Hua, Bangmin Han, Juntao Jiang, Yingjian Zhu, Yifeng Jing
Summary: Maternal exposure to dibutyl phthalate (DBP) induces renal fibrosis in offspring. The study investigated the role of connexin 43 (Cx43) in DBP-induced renal fibrosis. The results showed that DBP increased the expression of Cx43 in renal tubular epithelial cells (RTECs), and silencing Cx43 alleviated DBP-induced epithelial-mesenchymal transition (EMT) in HK-2 cells. Bioinformatics analysis revealed that DBP upregulated Cx43 expression through the Ang II/AMPK alpha 2 signaling pathway. These findings suggest that targeting Cx43 and the Ang II/AMPK alpha 2 pathway may be a potential treatment for renal fibrosis.
Article
Biochemistry & Molecular Biology
Chien-Hung Lin, Chuan Wan, Wen-Sheng Liu, Hsin-Hui Wang
Summary: Exposure to PM2.5 can induce EMT characteristics in HK-2 cells, with the IL-6/STAT3 pathway playing a key role in mediating early renal tubule cell injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yue Pu, Yao Wu, Yan Zhou, Li-hong Wan
Summary: Azithromycin (AZM) targets RACK1 to inhibit TGF-beta 1 mediated EMT in bronchial epithelial cells, leading to the suppression of cell migration and reversal of EMT.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Qi Wang, Fuqiang Wang, Xiangze Li, Zhi Ma, Dapeng Jiang
Summary: This study investigated the effect of quercetin treatment on renal fibrosis and its mechanism. The results showed that quercetin can alleviate fibrosis, inflammation, oxidative stress, and cell apoptosis. Quercetin alleviates fibrosis by inhibiting the activation of AREG/EGFR signaling.
PHYTOTHERAPY RESEARCH
(2023)
Review
Endocrinology & Metabolism
Jun-Qing Zhang, Ying-Ying Li, Xue-Yan Zhang, Zeng-Hui Tian, Cheng Liu, Shi-Tao Wang, Fa-Rong Zhang
Summary: Renal fibrosis is a common pathological manifestation of chronic kidney diseases and a major cause of end-stage renal disease, but its pathogenesis remains unclear. Renal tubular epithelial cell senescence has been found to accelerate the progression of renal fibrosis. Oxidative stress, telomere attrition, and DNA damage are the major causes of renal tubular epithelial cell senescence. Interventions and therapeutic strategies targeting cellular senescence, such as calorie restriction, exercise, Klotho, senolytics, and senostatics, show potential for the treatment of renal fibrosis.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Xunian Zhou, Fei Xiao, Hikaru Sugimoto, Bingrui Li, Kathleen M. McAndrews, Raghu Kalluri
Summary: By using genetically modified mice, researchers were able to simulate key genetic alterations found in renal cell carcinoma (RCC) and demonstrate the functional role of systemic inflammation and the tumor microenvironment in the development of malignant cancer from preestablished dysplastic precursor lesions.
Article
Medicine, General & Internal
Naiquan Liu, Dongyang Li, Dajun Liu, Ying Liu, Jing Lei
Summary: The study found that FOSL2 plays a crucial role in promoting renal fibrosis and is involved in the regulation of the SGK1 signaling pathway. Inhibiting FOSL2 may offer a potential strategy for the treatment of renal fibrosis.
JOURNAL OF TRANSLATIONAL INTERNAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Ying Liu, Dao-Hai Cheng, Ke-Dao Lai, Hua Su, Guo-Shou Lu, Li Wang, Ji-Hua Lv
Summary: Ventilagolin suppresses the migration, invasion, and EMT of HCC cells by downregulating Pim-1, showing potential therapeutic effects. In vivo experiments demonstrate that Ventilagolin effectively inhibits HCC tumor growth and regulates the expression of Pim-1 and EMT-related proteins.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Mei-Chuan Kuo, Wei-An Chang, Ling-Yu Wu, Yi-Chun Tsai, Ya-Ling Hsu
Summary: Hypoxia-induced epithelial-to-mesenchymal transition (EMT) in proximal tubular epithelial cells (PTECs) is modulated by miR-545-3p-TNFSF10 interaction. TNFSF10 attenuates EMT induced by hypoxia in PTECs. These findings provide new insights into the unique regulation of miR-545-3p-TNFSF10 interaction and their potential therapeutic effect in kidney injury induced by hypoxia.
Article
Anatomy & Morphology
Yonghong Lian, Cuiqiong Li, Jianchun Li, Yongxiang Xie, Qiancheng Liu, Minhua Wu, Wei Shi, Lifeng Meng
Summary: This study aimed to investigate the role of connexin 43 (Cx43) in regulating epithelial mesenchymal transformation (EMT) of renal tubular epithelial cells (RTECs) through the Akt/mTOR signaling pathway and the potential inhibitory effect of Astragaloside IV (ASV) on renal interstitial fibrosis by regulating Cx43. The results showed that Cx43 played a significant role in RTECs injury and that ASV could inhibit TGF-beta 1-induced RTECs transdifferentiation. Further investigation of this mechanism may provide promising therapeutic strategies for the treatment of renal interstitial fibrosis.
Article
Immunology
Lei Wu, Chao Rong, Qing Zhou, Xin Zhao, Xue-Mei Zhuansun, Shan Wan, Mao-Min Sun, Shou-Li Wang
Summary: This study showed that BM-MSCs attenuated cisplatin-induced renal fibrosis by regulating the miR-146a-5p/Tfdp2 axis in mRTECs. This provides a new direction for the treatment of chronic kidney diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuqin Tan, Tong Zheng, Rui Zhang, Suxiang Chen, Qingdi Cheng, Jinhua Zhang, Ruojiao Wang, Min Chen, Ning Na
Summary: This study elucidates the role of the APA writer CSTF2 in the process of renal fibrosis, demonstrating that CSTF2 is upregulated by TGF-beta and facilitates FGF2 overexpression to form a pro-fibrotic axis. These findings suggest that CSTF2 is a potentially promising target for renal fibrosis that does not directly disrupt TGF-beta signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Honoka Tanno, Takayuki Sassa, Megumi Sawai, Akio Kihara
Summary: Branched-chain fatty acids are important components in the meibum lipids secreted from the meibomian glands. Enzymes such as ELOVL1, ELOVL3, and ELOVL7 are responsible for elongating branched-chain acyl-CoAs. Liquid chromatography-tandem mass spectrometry has revealed the predominance of branched-chain lipids in mouse meibomian glands, demonstrating the significance of ELOVL1 in elongating branched-chain VLC acyl-CoAs in vivo.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Editorial Material
Dermatology
Takayuki Sassa, Yasutomo Imai, Akio Kihara, Kiyofumi Yamanishi
JOURNAL OF DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Koki Nojiri, Shuhei Fudetani, Ayami Arai, Takuya Kitamura, Takayuki Sassa, Akio Kihara
Summary: Sjogren-Larsson syndrome is a genetic neurocutaneous disorder caused by mutations in the ALDH3A2 gene. Research has found that the pathology mainly involves a decrease in acylceramide production. Experiments with double-knockout mice and human immortalized keratinocytes lacking ALDH3A2 demonstrated reduced acylceramide levels, providing insight into the development of the disease.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Correction
Multidisciplinary Sciences
Megumi Sawai, Keisuke Watanabe, Kana Tanaka, Wataru Kinoshita, Kento Otsuka, Masatoshi Miyamoto, Takayuki Sassa, Akio Kihara
Article
Clinical Neurology
Taiko Takahashi, Sevcan Mercan, Takayuki Sassa, Gunseli Bayram Akcapinar, Kanay Yararbas, Seda Susgun, Sibel Aylin Ugur Iseri, Akio Kihara, Nihan Hande Akcakaya
Summary: This study describes two siblings with cerebral palsy caused by an ELOVL1 splice site mutation. The mutation leads to exon skipping and significant changes in the lipid composition of the skin stratum corneum.
BRAIN & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Kento Otsuka, Megumi Sawai-Ogawa, Akio Kihara
Summary: Fatty acyl-CoA reductases (FARs) play a crucial role in the synthesis of meibum lipids, which are important for tear stability and eye health. This study reveals the specific functions of two FAR isozymes (FAR1 and FAR2) in the production of different chain lengths of fatty alcohols (FAls), and highlights the importance of FAl-containing meibum lipids in the formation of a functional tear film lipid layer.
Article
Biochemistry & Molecular Biology
Madoka Suzuki, Yusuke Ohno, Akio Kihara
Summary: This study used LC/MS/MS analysis to identify 1,327 unbound ceramides and 254 protein-bound ceramides in the stratum corneum. The researchers discovered a wide variety of ceramide species with different long-chain bases in the human skin, and demonstrated the production of specific long-chain bases by one of the enzymes. This study provides a molecular basis for understanding ceramide diversity in the skin and the pathogenesis of skin disorders.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Dermatology
Ayami Arai, Takuya Takeichi, Hiroyuki Wakamoto, Takayuki Sassa, Yasutoshi Ito, Yuya Murase, Tomoo Ogi, Masashi Akiyama, Akio Kihara
Summary: Sjogren-Larsson syndrome (SLS) is a neurocutaneous disorder characterized by ichthyosis. This study identified a duplication and a missense mutation in the ALDH3A2 gene of an SLS patient, leading to reduced levels of acylceramides. The findings suggest that the reduction in acylceramide levels may be the primary cause of the ichthyosis symptoms in SLS.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Article
Dermatology
Tomohiro Nohara, Yusuke Ohno, Akio Kihara
Summary: This study validates the involvement of PNPLA1 gene mutations in the pathogenesis of congenital ichthyosis and reveals the correlation between these mutations' effects on acylceramide production and the disease's pathology.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Editorial Material
Ophthalmology
Yuki Hamada, Lena Sasaki, Hikari Uehara, Tomo Suzuki, Shigeru Kinoshita, Kento Otsuka, Akio Kihara, Yoshiaki Yamaguchi, Takahito Miyake, Masao Doi
Article
Biochemistry & Molecular Biology
Satarupa Bhaduri, Analine Aguayo, Yusuke Ohno, Marco Proietto, Jasmine Jung, Isabel Wang, Rachel Kandel, Narinderbir Singh, Ikran Ibrahim, Amit Fulzele, Eric J. Bennett, Akio Kihara, Sonya E. Neal
Summary: This study reveals the association between the pseudoprotease Dfm1 and the SPOTS complex, highlighting their roles in sphingolipid metabolism. Additionally, Dfm1 is found to play a crucial role in the ER export and degradation of Orm2. These findings provide insights into the molecular mechanisms underlying sphingolipid metabolism and its implications in disease.
Article
Cell Biology
Yasuhiro Hirano, Yusuke Ohno, Yoshino Kubota, Tatsuo Fukagawa, Akio Kihara, Tokuko Haraguchi, Yasushi Hiraoka
Summary: Recent studies have revealed that enzymes catalyzing lipid synthesis play a role in maintaining the integrity of the nuclear envelope (NE), but the mechanism involved remains unclear. In this study, the ceramide synthase homolog, Tlc4, was found to suppress NE defects in cells lacking the NE proteins Lem2 and Bqt4. Tlc4, which possesses a conserved TRAM/LAG1/CLN8 domain, functions through its non-catalytic activity and localizes at the NE, endoplasmic reticulum, and cisand medial-Golgi cisternae. The Golgi localization of Tlc4 is closely linked to its activity of suppressing NE defects in the double-deletion mutant of Lem2 and Bqt4.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yuka Tamura, Takayuki Sassa, Takumi Nishizawa, Akio Kihara
Summary: This article mainly discusses spinocerebellar ataxias (SCAs), which are autosomal dominant diseases characterized by cerebellar atrophy and ataxia. It focuses on the SCA34 subtype, which is caused by specific mutations in the ELOVL4 gene. The study shows that these mutations lead to the production of shorter ultra-long-chain polyunsaturated fatty acids (ULC-PCs) in neurons, which may contribute to the pathogenesis and dominant inheritance of SCA34.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hirotaka Goto, Masatoshi Miyamoto, Akio Kihara
Summary: S1P is primarily taken up by cells after dephosphorylation by PLPPs, but there is also a PLPP-independent pathway for S1P uptake. The existence of direct S1P uptake pathway was confirmed through tracer experiments and overexpression/knockout of specific transporters.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Madoka Suzuki, Yusuke Ohno, Akio Kihara
Summary: This study conducted LC/MS/MS analyses to reveal various ceramide species in the human stratum corneum, quantifying a large number of ceramides and providing a molecular basis for understanding the diversity of human skin ceramides and the pathogenesis of skin disorders.
JOURNAL OF LIPID RESEARCH
(2022)