AI Article Synopsis
- Focal segmental glomerulosclerosis (FSGS) is characterized by damage to podocytes, which are specialized kidney cells essential for filtering blood.
- A specific protein kinase, ROCK2, was found to be activated in both FSGS mice and cultured podocytes exposed to adriamycin (ADR), a drug that induces FSGS.
- Mice with a knockout of the ROCK2 gene in podocytes showed resistance to kidney damage, and using a ROCK2 inhibitor improved podocyte health and reduced kidney scarring, suggesting that targeting ROCK2 could be a promising treatment for FSGS.
Article Abstract
Focal segmental glomerulosclerosis (FSGS) shares podocyte damage as an essential pathological finding. Several mechanisms underlying podocyte injury have been proposed, but many important questions remain. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) is a serine/threonine kinase responsible for a wide array of cellular functions. We found that ROCK2 is activated in podocytes of adriamycin (ADR)-induced FSGS mice and cultured podocytes stimulated with ADR. Conditional knockout mice in which the ROCK2 gene was selectively disrupted in podocytes (PR2KO) were resistant to albuminuria, glomerular sclerosis, and podocyte damage induced by ADR injection. In addition, pharmacological intervention for ROCK2 significantly ameliorated podocyte loss and kidney sclerosis in a murine model of FSGS by abrogating profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor proved that ROCK2 is a cyclic nucleotide signaling pathway regulator. Our study highlights the potential utility of ROCK2 inhibition as a therapeutic option for FSGS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987559 | PMC |
| http://dx.doi.org/10.1038/s42003-024-06127-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Molecular mechanism of Xiangsha Liujunzi Decoction in treating chronic atrophic gastritis based on transcriptome sequencing technology].
Zhongguo Zhong Yao Za Zhi
September 2024
Key Laboratory of Traditional Chinese Medicine for Prevention and Control of Regional High Incidence Diseases in Ningxia,Ministry of Education, Ningxia Medical University Yinchuan 750004, China.
Based on transcriptomics technology, this study investigated the molecular mechanisms of Xiangsha Liujunzi Decoction in treating chronic atrophic gastritis(CAG), which were confirmed through experimental validation. The CAG rat model was built by the MNNG composite multi-factor method, followed by a 90-day administration of Xiangsha Liujunzi Decoction. The study measured the rat body mass and 3-hour food intake in each group and observed the pathological changes in gastric tissue using HE staining.
View Article and Find Full Text PDForexin B alleviates sepsis-associated lung injury through the attenuation of pulmonary endothelial barrier dysfunction by regulating the rho-associated coiled-coil containing protein kinase 2/zonula occludens-1 (ROCK2/ZO-1) axis.
Biotechnol Appl Biochem
December 2024
Department of Emergency Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Dysfunction of the alveolar endothelial barrier plays a crucial role in the pathogenesis of septic acute lung injury (ALI). orexin B is a neuropeptide derived from orexin neurons in the lateral hypothalamus and has multiple biological functions. However, the physiological function of orexin B in sepsis is less reported.
View Article and Find Full Text PDFHydroxysafflor yellow A, a natural food pigment, ameliorates atherosclerosis in ApoE mice by inhibiting the SphK1/S1P/S1PR3 pathway.
Food Sci Nutr
November 2024
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Key Laboratory of Metabolic Disease Prevention and Treatment of Traditional Chinese Medicine, Institute of Chinese Medicine Guangdong Pharmaceutical University Guangzhou Guangdong China.
Atherosclerosis (AS) is the pathologic basis of many cardiovascular diseases (CVDs). Hydroxysafflor yellow A (HSYA) is a valuable natural food pigment that has been reported to have significant health-promoting abilities. However, the anti-AS efficacy and mechanisms of HSYA have not yet been characterized.
View Article and Find Full Text PDFEffect of silencing Ras homolog family member C on proliferation, invasion, and migration of salivary adenoid cystic carcinoma.
Hua Xi Kou Qiang Yi Xue Za Zhi
December 2024
Institute of Stomatology, Binzhou Medical University, Yantai 264000, China.
Objectives: This study aimed to investigate the effects of silencing Ras homolog family member C (RhoC) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of salivary adenoid cystic carcinoma (SACC) and its molecular mechanisms.
Methods: A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1, 2019 to March 1, 2024 were selected, and the expression levels of RhoC were detected by Western blot and immunohistochemistry. Three small interfering RNA (siRNAs) were designed to target the RhoC gene sequence, transfected into SACC-LM and SACC-83 cell lines, and evaluated for transfection efficiency.
Exploring the Role of ROCK Inhibition in Corneal Edema Through Crosstalk Between Epithelial and Endothelial Cells.
J Ophthalmol
November 2024
School of Medicine, Tzu Chi University, Hualien, Taiwan.
The maintenance of corneal transparency and normal vision is dependent on preservation of epithelial and endothelial cell layer homeostases. Different types of corneal injury can induce swelling and losses in transparency. Fuchs endothelial corneal dystrophy (FECD) is one type of injury that is commonly treated with rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!