Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats

Zheng, Long; Li, Long; Qi, Guisheng; Hu, Mushuang; Hu, Chao; Wang, Shuo; Li, Jiawei; Zhang, Mingnan; Zhang, Weitao; Zeng, Yanwu; Zhang, Yi; Li, Liping; Wang, Xuanchuan; Lin, Miao; Zhu, Tongyu; Rong, Ruiming

doi:10.1159/000489445

Cited by 21 publications

(23 citation statements)

References 44 publications

(44 reference statements)

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“…In greater detail, Olga simionescu and colleagues demonstrated that telocytes maintained in close contact with mast cells, macrophages and mononuclear cells by their long telopode and an apoptotic telocyte with condensed chromatin has been found in the vicinity of a dendritic cell in psoriasis . Although a few studies have reported the function of telocytes, little is known about the relationship between telocytes and other cells. We found that the level of iNOS was significantly increased after TLR2 activation (Figure C,), suggesting that activated telocytes had enhanced the ability of immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Li¹,

Shen²,

He³

2019

J Cellular Molecular Medi

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Telocytes, newly discovered in the last decade, are interstitial cells found in numerous organs, with multiple proposed potential biological functions. Toll‐like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen‐associated molecular patterns (PAMPs). However, it is still unknown whether telocytes express these innate receptors. We sought to determine the expression and role of TLRs in telocytes. In our study, we primarily detected TLR1‐9 expression in telocytes. The proliferation, apoptosis and immunoregulatory activity of telocytes activated with or without TLR ligands were determined. Our results showed that purified telocytes expressed TLR2, TLR3 and TLR5. In particular, telocytes expressed high levels of TLR2 as observed using flow cytometry. When we stimulated telocytes with TLR2 or TLR3 agonists (Pam3CSK4, PolyI:C), iNOS expression was greatly increased after Pam3CSK4 treatment. Additionally, telocyte proliferation was reduced and cell apoptosis was increased after TLR agonist stimulation. A co‐culture experiment showed that supernatant from telocytes pretreated with Pam3CSK4 inhibited T cell activation much more than that from untreated telocytes and this effect was mediated by iNOS. Overall, our results demonstrated TLR expression on telocytes for the first time and provided evidence of an immunoregulatory role of telocytes, indicating their clinical potential.

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Section: Discussionmentioning

confidence: 99%

Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Li¹,

Shen²,

He³

2019

J Cellular Molecular Medi

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“…Associated pathologies/dysfunctions Kidneys Renal cortex (Qi et al, 2012), Interstitium and renal capsule (Zheng et al, 2012) Macrophages blood vessels (Zheng et al, 2012) Erythropoiesis stromal tissue (Imeri et al, 2019), Organization/maintenance (Zheng et al, 2012) Myxomas (Mandache & Penescu, 2015), Ischemia (Li et al, 2014), Renal fibrosis (Zheng et al, 2018) Renal Pelvis Interstitium (Gevaert et al, 2012) Nerve endings blood vessels (Gevaert et al, 2012) ER signaling pathway (Gevaert et al, 2012) Unclear Ureters Lamina Propria, Sheath of Waldeyer (Rusu et al, 2018b) Epithelial cells nerve endings blood vessels (Rusu et al, 2018b;Zheng et al, 2012) Stem/progenitor niche (Dobra et al, 2018), Stromal tissue organization/maintenance (Zheng et al, 2012) Hydronephrosis (Wolnicki et al, 2019)…”

Section: Possible Functionsmentioning

confidence: 99%

“…However, this protective effect occurs through an inflammation‐independent pathway, possibly due to the production of growth factors capable of promoting the proliferation of epithelial cells in the renal tubules (Li et al, 2014). In cases of fibrosis‐induced experiments, there is evidence that the transplantation of telocytes could attenuate characteristic stromal changes, downregulating the proliferation of myofibroblasts, as well as decreasing serum levels of TGFβ1 and increasing levels of hepatocyte growth factor (Zheng et al, 2018). This factor prevents epithelial cell death and also enhances regeneration of renal tissue after injury (Matsumoto & Nakamura, 2001).…”

Section: Male Urinary Tractmentioning

confidence: 99%

Telocytes of the male urogenital system: Interrelationships, possible functions, and pathological implications

Sanches

Tamarindo

Maldarine

et al. 2021

Cell Biology International

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The male urogenital system is composed of the reproductive system and the urinary tract; they have an interconnected embryonic development and share one of their anatomical components, the urethra. This system has a highly complex physiology deeply interconnected with the circulatory and nervous systems, as well as being capable of adapting to environmental variations; it also undergoes changes with aging and, in the case of the reproductive system, with seasonality.The stroma is an essential component in this physiological plasticity and its complexity has increased with the description in the last decade of a new cell type, the telocyte. Several studies have demonstrated the presence of telocytes in the organs of the male urogenital system and other systems; however, their exact function is not yet known. The present review addresses current knowledge about telocytes in the urogenital system in terms of their locations, interrelationships, possible functions and pathological implications. It has been found that telocytes in the urogenital system possibly have a leading role in stromal tissue organization/maintenance, in addition to participation in stem cell niches and an association with the immune system, as well as specific functions in the urogenital system, lipid synthesis in the testes, erythropoiesis in the kidneys and the micturition reflex in the bladder. There is also evidence that telocytes are involved in pathologies in the kidneys, urethra, bladder, prostate, and testes.

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“…Western blot analysis was performed as described previously (29). Briefly, the total protein was extracted from kidney tissue samples or cultured cells (15 mg each) and separated using electrophoresis.…”

Section: Western Blot Analysismentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

Qiu¹,

Cao²,

Tu³

et al. 2021

Front. Immunol.

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BackgroundRenal fibrosis is inevitable in all progressive chronic kidney diseases (CKDs) and represents a serious public health problem. Immune factors contribute to the progression of renal fibrosis. Thus, it is very possible that immunosuppression cells, such as myeloid-derived suppressor cells (MDSCs), could bring benefits to renal fibrosis. Herein, this study investigated the antifibrotic and reno-protective effect of MDSCs and the possible mechanisms.MethodsMurine and cell models of unilateral ureter obstruction (UUO) renal fibrosis were used. Bone marrow-induced MDSCs and granulocyte–macrophage colony-stimulating factor (GM-CSF) were pretreated before surgery. Kidney weight, pathological injury, extracellular matrix deposition, and epithelial–mesenchymal transition progression were examined. Transforming growth factor (TGF)-β1)/Smad/Snail signaling pathway involvement was investigated through Western blotting and quantitative PCR (qPCR). Accumulation of MDSC, CD4+ T cell, regulatory T (Treg), and T helper 1 (TH1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry.ResultsIn vitro- and in vivo-induced MDSCs significantly ameliorated UUO-induced tubulointerstitial fibrosis, inhibited the TGF-β1/Smad/Snail signaling pathway, and enhanced MDSC and Treg infiltration in the kidney while downregulating the TH1 cells. Both in vitro and in vivo experiments confirmed CCL5 elevation in the two MDSC-treated groups.ConclusionIn vitro- and in vivo-induced MDSCs alleviated renal fibrosis similarly through promoting the CCL5–CCR5 axis interaction and TGF-β1/Smad/Snail signaling pathway inhibition. Our results indicate an alternative treatment for renal fibrosis.

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Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats

Cited by 21 publications

References 44 publications

Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Telocytes of the male urogenital system: Interrelationships, possible functions, and pathological implications

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

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