8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Salvianolic acid B (Sal B) is one of the main water-soluble components of Salvia miltiorrhiza Bge. Numerous reports have demonstrated that it could exert significant renal-protective effects, but the underlying mechanism remains unclear. The present study demonstrated that Sal B could alleviate renal injury by regulating the heparanase/syndecan-1 (HPSE/SDC1) axis. In vivo, the serum creatinine, blood urea nitrogen, transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) levels, and the histopathological changes of mice kidneys were examined. Sal B could notably reduce the renal injury caused by left ureteral ligation. In vitro, Sal B downregulated the expression levels of HPSE/FGF-2/TGF-β1/α-smooth muscle actin and upregulated the expression levels of SDC1/E-cadherin in angiotensin II-stimulated HK-2 cells in a dose-dependent manner. In summary, to the best of the authors' knowledge, the present study provided evidence for the first time that Sal B could exert renal-protective effects via the inhibition of the HPSE/SDC1 axis, and these results suggest that the administration of Sal B may be a novel therapeutic strategy in treating renal interstitial fibrosis.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          The origin of renal fibroblasts/myofibroblasts and the signals that trigger fibrosis.

          Renal fibrosis is a common characteristic of chronic kidney disease (CKD). Aberrant and excessive depositions of extracellular matrix (ECM) proteins in both glomeruli and interstitial regions are typical hallmarks of renal fibrosis and amplify the severity of kidney injury. To date, an approved therapy specifically targeted to renal fibrosis is needed to mitigate or even retard renal fibrosis. Recent findings have identified a unique population of myofibroblasts as a primary source of ECM in scar tissue formation. However, the origin of myofibroblasts in renal fibrosis remains the subject of controversial debates. The advancement in lineage tracing and immunofluorescent microscopy technologies have suggested that myofibroblasts may arise from a number of sources such as activated renal fibroblasts, pericytes, epithelial-to-mesenchymal transition (EMT), endothelial-to-mesenchymal transition (EndoMT), bone marrow derived cells and fibrocytes. Recent studies also indicate that multiple ligands of TGF-β/Smads are the direct mediators for renal fibrosis. Consistently, inhibition of the TGF-β/Smads signaling pathway using various strategies significantly reduce renal fibrotic lesions and ameliorate kidney injury, suggesting that targeting the TGF-β/Smads signaling pathway could be a new strategy for effective therapies. In this review, we will briefly discuss the diverse origins of myofibroblasts and molecular pathways triggering renal fibrosis. Prospective therapeutic approaches based on those molecular mechanisms will hopefully offer exciting insights in the development of new therapeutic interventions for patients in the near future.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Signalling pathways involved in hypoxia‐induced renal fibrosis

            Abstract Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end‐stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia‐induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia‐inducible signalling pathways and complex interactive networks. Therefore, this review will focus on the signalling pathways involved in hypoxia‐induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF, TGF‐β, Notch, PKC/ERK, PI3K/Akt, NF‐κB, Ang II/ROS and microRNAs. Roles of molecules such as IL‐6, IL‐18, KIM‐1 and ADO are also reviewed. A comprehensive understanding of the roles that these hypoxia‐responsive signalling pathways and molecules play in the context of renal fibrosis will provide a foundation towards revealing the underlying mechanisms of progression of CKD and identifying novel therapeutic targets. In the future, promising new effective therapy against hypoxic effects may be successfully translated into the clinic to alleviate renal fibrosis and inhibit the progression of CKD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Myofibroblast in Kidney Fibrosis: Origin, Activation, and Regulation.

              Renal fibrosis is characterized by excessive deposition of extracellular matrix (ECM), leading to destruction of normal kidney architecture and loss of renal function. The activation of α-smooth muscle actin-positive myofibroblasts plays a key role in this process. After kidney injury, profibrotic factors are secreted by injured tubular epithelia and infiltrated inflammatory cells to promote complex cascades of signaling events leading to myofibroblastic activation, proliferation, and ECM production. The origins of myofibroblasts remain controversial, and possibilities include resident fibroblasts, pericytes, bone marrow-derived cells, and endothelial cells. Recent evidence supports the existence of localized fibrogenic niches, which provides a specialized tissue microenvironment for myofibroblastic activation and expansion. Myofibroblasts often undergo epigenetic modifications, leading to their sustained activation and resistance to apoptosis. In this chapter, we discuss the origins, heterogeneity, and activation of myofibroblasts in diseased kidneys. We also highlight novel strategies for the treatment of patients with fibrotic kidney diseases.
                Bookmark

                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                August 2020
                15 June 2020
                15 June 2020
                : 22
                : 2
                : 1325-1334
                Affiliations
                Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
                Author notes
                Correspondence to: Professor Li Xu, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia, Nanjing, Jiangsu 210023, P.R. China, E-mail: xuli64@ 123456163.com
                [*]

                Contributed equally

                Article
                MMR-22-02-1325
                10.3892/mmr.2020.11229
                7339410
                32626974
                d70ea531-5978-43af-8f53-8eb6158d718e
                Copyright: © Hu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 16 December 2019
                : 28 May 2020
                Categories
                Articles

                salvianolic acid b,renal interstitial fibrosis,heparanase,syndecan-1,angiotensin ii

                Comments

                Comment on this article