Renal fibrosis in type 2 cardiorenal syndrome: An update on mechanisms and therapeutic opportunities

Xu, Xia; Zhang, Bingxuan; Wang, Yajiao; Shi, Shuqing; Lv, Jiayu; Fu, Zhenyue; Gao, Xiya; Li, Yumeng; Wu, Huaqin; Song, Qingqiao

doi:10.1016/j.biopha.2023.114901

Cited by 5 publications

(5 citation statements)

References 203 publications

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“…Our findings revealed that knockdown of integrin αvβ5 in skeletal muscles exacerbated cardiac depression in response to hemorrhage, which may be related to circulating cytokine changes following knockdown of muscle integrin αvβ5. Cross-talk exists between either skeletal muscles and the myocardium or between other organs contributing to the modulation of cardiac performance ( Call et al, 2015 ; Xu et al, 2023 ), which also supports our finding of the protective effects of integrin αvβ5 in skeletal muscles and cardiac performance in response to hemorrhage.…”

Section: Discussionsupporting

confidence: 89%

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage

Wang,

Kulthinee,

Slate-Romano

et al. 2023

Experimental and Molecular Pathology

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Section: Discussionsupporting

confidence: 89%

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage

Wang,

Kulthinee,

Slate-Romano

et al. 2023

Experimental and Molecular Pathology

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“…CKD and ESRD are major public health problems with increasing prevalence worldwide and in the US almost 15% (37 million) people are suffering from CKD ( 28 , 29 ). Unfortunately, at present, there are no effective therapies to prevent or slow the progression of renal inflammation and fibrosis, and the treatment options for patients with ESRD are limited to dialysis and renal transplant ( 4 – 6 ). The lack of novel drugs targeting the pathological events of renal inflammation and fibrosis often give mixed results with unwanted side effects ( 5 , 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, at present, there are no effective therapies to prevent or slow the progression of renal inflammation and fibrosis, and the treatment options for patients with ESRD are limited to dialysis and renal transplant ( 4 – 6 ). The lack of novel drugs targeting the pathological events of renal inflammation and fibrosis often give mixed results with unwanted side effects ( 5 , 6 ). The shortcomings of these experimental therapies are likely due to the fact that the pathogenesis of fibrosis is complex.…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the current therapeutic choices for the clinical management and treatment of CKD ( 8 ). However, these mainstay treatment options have limited efficacy to prevent or treat renal fibrosis, the major pathological event that leads to the progression of CKD to ESRD ( 5 , 6 ). More recently, finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, has been demonstrated to decrease albuminuria and risk of CKD progression in chronic heart failure and diabetes ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…There is an unmet need of novel combined anti-inflammatory and anti-fibrotic agents, particularly as an effective therapeutic approach for CKD and its progression to ESRD (5)(6)(7). Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the current therapeutic choices for the clinical management and treatment of CKD (8).…”

Section: Introductionmentioning

confidence: 99%

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Dual soluble epoxide hydrolase inhibitor – farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis

Khan,

Nolan,

Stavniichuk

et al. 2024

Front. Immunol.

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IntroductionRenal fibrosis associated with inflammation is a critical pathophysiological event in chronic kidney disease (CKD). We have developed DM509 which acts concurrently as a farnesoid X receptor agonist and a soluble epoxide hydrolase inhibitor and investigated DM509 efficacy as an interventional treatment using the unilateral ureteral obstruction (UUO) mouse model.MethodsMale mice went through either UUO or sham surgery. Interventional DM509 treatment (10mg/kg/d) was started three days after UUO induction and continued for 7 days. Plasma and kidney tissue were collected at the end of the experimental protocol.ResultsUUO mice demonstrated marked renal fibrosis with higher kidney hydroxyproline content and collagen positive area. Interventional DM509 treatment reduced hydroxyproline content by 41% and collagen positive area by 65%. Renal inflammation was evident in UUO mice with elevated MCP-1, CD45-positive immune cell positive infiltration, and profibrotic inflammatory gene expression. DM509 treatment reduced renal inflammation in UUO mice. Renal fibrosis in UUO was associated with epithelial-to-mesenchymal transition (EMT) and DM509 treatment reduced EMT. UUO mice also had tubular epithelial barrier injury with increased renal KIM-1, NGAL expression. DM509 reduced tubular injury markers by 25-50% and maintained tubular epithelial integrity in UUO mice. Vascular inflammation was evident in UUO mice with 9 to 20-fold higher ICAM and VCAM gene expression which was reduced by 40-50% with DM509 treatment. Peritubular vascular density was reduced by 35% in UUO mice and DM509 prevented vascular loss.DiscussionInterventional treatment with DM509 reduced renal fibrosis and inflammation in UUO mice demonstrating that DM509 is a promising drug that combats renal epithelial and vascular pathological events associated with progression of CKD.

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Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model

Kuo,

Chuang,

Chen

et al. 2024

European Journal of Pharmacology

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Renal fibrosis in type 2 cardiorenal syndrome: An update on mechanisms and therapeutic opportunities

Cited by 5 publications

References 203 publications

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage

Dual soluble epoxide hydrolase inhibitor – farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model

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