bims-raghud 2024-09-15 papers

Issue of 2024–09–15
two papers selected by
Irene Sambri, TIGEM

Zool Res. 2024 Sep 18. pii: 2095-8137(2024)05-1161-14. [Epub ahead of print]45(5): 1161-1174

Experimental models for preclinical research in kidney disease.

Jin Miao, Huanhuan Zhu, Junni Wang, Jianghua Chen, Fei Han, Weiqiang Lin.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are significant public health issues associated with a long-term increase in mortality risk, resulting from various etiologies including renal ischemia, sepsis, drug toxicity, and diabetes mellitus. Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases. Among these, rodent models have proven to be powerful tools in the discovery of novel therapeutics, while the development of kidney organoids has emerged as a promising advancement in the field. This review provides a comprehensive analysis of the construction methodologies, underlying biological mechanisms, and recent therapeutic developments across different AKI and CKD models. Additionally, this review summarizes the advantages, limitations, and challenges inherent in these preclinical models, thereby contributing robust evidence to support the development of effective therapeutic strategies.

Keywords: Acute kidney injury; Chronic kidney disease; Mouse models

DOI: https://doi.org/10.24272/j.issn.2095-8137.2024.072

EMBO Rep. 2024 Sep 13.

mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis.

Angus T Stock, Sarah Parsons, Jacinta A Hansen, Damian B D'Silva, Graham Starkey, Aly Fayed, Xin Yi Lim, Rohit D'Costa, Claire L Gordon, Ian P Wicks.

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts-in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis-coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.

Keywords: Kawasaki Disease; Myofibroblasts; Stenosis; Vasculitis; mTOR

DOI: https://doi.org/10.1038/s44319-024-00251-1