Analyses of damage-associated molecular patterns, particularly biglycan, in cisplatin-induced rat progressive renal fibrosis

Damage-associated molecular patterns (DAMPs) and their receptors (TLR-2 and -4) may play important roles in renal fibrosis, of which the pathogenesis is complicated. We used rat renal lesions induced by a single intraperitoneal injection of cisplatin at 6 mg/kg body weight; consisting of tissue dama...

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Bibliographic Details
Published in:Journal of Toxicologic Pathology 2023, Vol.36(3), pp.181-185
Main Authors: Nakagawa, Minto, Izawa, Takeshi, Kuwamura, Mitsuru, Yamate, Jyoji
Format: Article
Language:English
Subjects:
biglycan
Body weight
Cisplatin
Damage patterns
damage-associated molecular patterns
Extracellular matrix
Fibrinogen
Fibronectin
Fibrosis
Heat shock proteins
Immune system
Inflammation
Kidneys
Laminin
Lesions
Leucine
Macrophages
Pathogenesis
Proteoglycans
rat renal fibrosis
Renal tubules
Short Communication
TLR-2
TLR-4
TLR2 protein
Toll-like receptors
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Summary:Damage-associated molecular patterns (DAMPs) and their receptors (TLR-2 and -4) may play important roles in renal fibrosis, of which the pathogenesis is complicated. We used rat renal lesions induced by a single intraperitoneal injection of cisplatin at 6 mg/kg body weight; consisting of tissue damage of renal tubules on days 1 and 3, further damage and regeneration with inflammation mainly on days 5 and 7, and interstitial fibrosis on days 9, 12, 15, and 20. Microarray analyses on days 5 (the commencement of inflammation) and 9 (the commencement of interstitial fibrosis) showed that DAMPs increased by more than two-fold relative to control included common extra-cellular matrix (ECM) components such as laminin (Lamc2) and fibronectin, and heat shock protein family, as well as fibrinogen, although it was limited analysis; Lamc2, an element of basement membrane, may be regarded as an indicator for damaged renal tubules. In the real-time RT-PCR analyses, TLR-2 significantly increased transiently on day 1, whereas TLR-4 significantly increased on days 9 and 15, almost in agreement with the increased biglycan (a small leucine-rich proteoglycan as ubiquitous ECM component). As M1/M2 macrophages participated in renal lesions, such as inflammation and fibrosis, presumably, TLR-4, which may be expressed in immune cells, could play crucial roles in the formation of renal lesions in association with biglycan.
ISSN:0914-9198
1881-915X
1347-7404
DOI:10.1293/tox.2022-0148