RESUMEN
BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.
Asunto(s)
Apoptosis , Ratones Noqueados , Músculo Esquelético , Daño por Reperfusión , Transducción de Señal , Canal Catiónico TRPC6 , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Canal Catiónico TRPC6/metabolismo , Canal Catiónico TRPC6/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Calcio/metabolismoRESUMEN
OBJECTIVE: To explore the association between polymorphisms in the DNA repair gene, xeroderma pigmentosum group D (XPD), and development of hepatocellular carcinoma (HCC) in the Chinese population by performing a systematic review of the previously published clinical data. METHOD: A comprehensive literature search of the BIOSIS Previews and PubMed databases was carried out to identify all case-control studies of XPD polymorphisms and HCC risk. Meta-analysis was conducted to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) of developing HCC for carriers of the various XPD polymorphisms. RESULTS: Six case-control studies were selected for this meta-analysis, and comprised a total of 3424 HCC cases and 3636 controls. The pooled ORs (95% CIs) of XPD codon 751 and 312 allelomorphs were 1.25 (0.70 to 2.24) and 0.85 (0.58 to 1.25), respectively. Compared with the XPD wild-type homozygote Lys/Lys genotype of codon 751, the pooled OR (95% CI) of Lys/G1n + Gln/Gln genotypes for HCC risk was 1.31 (0.71 to 2.42). Compared with the XPD wild-type homozygote Asp/Asp genotype of codon 312, the pooled OR (95% CI) of Asp/Asn + Asn/Asn genotypes for HCC risk was 1.19 (0.73 to 1.95). CONCLUSION: Polymorphisms in the XPD codons 751 and 312 are not associated with HCC risk in the Chinese population.