ArticleInternational journal of molecular sciences2017
Anti-Fibrotic Effect of Losartan, an Angiotensin II Receptor Blocker, Is Mediated through Inhibition of ER Stress via Up-Regulation of SIRT1, Followed by Induction of HO-1 and Thioredoxin.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- HOXA2 exerts anti-renal fibrosis effects through reducing endoplasmic reticulum stress via the upregulation of SIRT1.Communications biology · 2025Article
- Class-Specific Effects of ARBs Versus ACE Inhibitors on Survival and Cardiovascular Outcomes in MASLD.International journal of molecular sciences · 2025Article
- Review
- Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.Kidney research and clinical practice · 2024Article
- Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis.Scientific reports · 2023Article
- Evolutionarily Conserved Role of Thioredoxin Systems in Determining Longevity.Antioxidants (Basel, Switzerland) · 2023Review
- Effects of Adjunct Antifibrotic Treatment within a Regenerative Rehabilitation Paradigm for Volumetric Muscle Loss.International journal of molecular sciences · 2023Article
- Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling.International journal of medical sciences · 2023Article
- Interleukin-10 Protects against Ureteral Obstruction-Induced Kidney Fibrosis by Suppressing Endoplasmic Reticulum Stress and Apoptosis.International journal of molecular sciences · 2022Article
- Review
- 5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction.International journal of molecular sciences · 2021Article
- The Prognosis of Arthrofibroses: Prevalence, Clinical Shortcomings, and Future Prospects.Trends in pharmacological sciences · 2021Review
- Endothelial Glycocalyx as a Regulator of Fibrotic Processes.International journal of molecular sciences · 2021Review
- Sirtuins at the Service of Healthy Longevity.Frontiers in physiology · 2021Review
- Tengdan Capsule Prevents Hypertensive Kidney Damage in SHR by Inhibiting Periostin-Mediated Renal Fibrosis.Frontiers in pharmacology · 2021Article
- Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy.Matrix biology plus · 2020Article
- Decreased Urinary Levels ofInternational journal of molecular sciences · 2020Article
- Endoplasmic reticulum stress is activated in post-ischemic kidneys to promote chronic kidney disease.EBioMedicine · 2018Article
- Sirtuins in Renal Health and Disease.Journal of the American Society of Nephrology : JASN · 2018Review
- Sex-specific differences in hypertension and associated cardiovascular disease.Nature reviews. Nephrology · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1) hemeoxygenase-1 (HO-1)/thioredoxin pathway. Renal tubular cells, tunicamycin (TM)-induced ER stress, and unilateral ureteral obstruction (UUO) mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-β, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α), through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor). Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.
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