Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin

Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reporte...

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Veröffentlicht in:American journal of physiology: endocrinology and metabolism 2021-02, Vol.320 (2), p.E179-E190
Hauptverfasser: Tsugawa-Shimizu, Yuri, Fujishima, Yuya, Kita, Shunbun, Minami, Satoshi, Sakaue, Taka-Aki, Nakamura, Yuto, Okita, Tomonori, Kawachi, Yusuke, Fukada, Shiro, Namba-Hamano, Tomoko, Takabatake, Yoshitsugu, Isaka, Yoshitaka, Nishizawa, Hitoshi, Ranscht, Barbara, Maeda, Norikazu, Shimomura, Iichiro
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container_end_page E190
container_issue 2
container_start_page E179
container_title American journal of physiology: endocrinology and metabolism
container_volume 320
creator Tsugawa-Shimizu, Yuri
Fujishima, Yuya
Kita, Shunbun
Minami, Satoshi
Sakaue, Taka-Aki
Nakamura, Yuto
Okita, Tomonori
Kawachi, Yusuke
Fukada, Shiro
Namba-Hamano, Tomoko
Takabatake, Yoshitsugu
Isaka, Yoshitaka
Nishizawa, Hitoshi
Ranscht, Barbara
Maeda, Norikazu
Shimomura, Iichiro
description Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for platelet-derived growth factor receptor β (PDGFRβ), surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-knockout (Tcad-KO) mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R-injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin. In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. In vitro, adiponectin promoted exosome secretion from mouse primary pericytes in a T-cadherin-dependent manner. Adiponectin plays an important role in maintaining the capillary network and amelioration of renal tubular injury by binding to T-cadherin.
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Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for platelet-derived growth factor receptor β (PDGFRβ), surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-knockout (Tcad-KO) mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R-injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin. In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. 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In addition, in response to I/R-injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin. In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. 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Fujishima, Yuya ; Kita, Shunbun ; Minami, Satoshi ; Sakaue, Taka-Aki ; Nakamura, Yuto ; Okita, Tomonori ; Kawachi, Yusuke ; Fukada, Shiro ; Namba-Hamano, Tomoko ; Takabatake, Yoshitsugu ; Isaka, Yoshitaka ; Nishizawa, Hitoshi ; Ranscht, Barbara ; Maeda, Norikazu ; Shimomura, Iichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-4e7c16ba0fa34a9b1e5d1143cdf0e40b36551e348a322d9c2fab77b0f7e4d4b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adipocytes</topic><topic>Adiponectin</topic><topic>Adiponectin - genetics</topic><topic>Animals</topic><topic>Cadherins</topic><topic>Cadherins - genetics</topic><topic>Capillaries</topic><topic>Capillary Permeability - genetics</topic><topic>Cells, Cultured</topic><topic>Damage</topic><topic>Glycosylphosphatidylinositol</topic><topic>Growth factors</topic><topic>Immunofluorescence</topic><topic>Injuries</topic><topic>Ischemia</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - etiology</topic><topic>Kidney Diseases - genetics</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Tubules - pathology</topic><topic>Kidneys</topic><topic>Male</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Muscles</topic><topic>Pericytes</topic><topic>Permeability</topic><topic>Phenotypes</topic><topic>Platelet-derived growth factor</topic><topic>Progenitor cells</topic><topic>Proteins</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - complications</topic><topic>Reperfusion Injury - genetics</topic><topic>Reperfusion Injury - pathology</topic><topic>Rodents</topic><topic>Severity of Illness Index</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>T-cadherin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsugawa-Shimizu, Yuri</creatorcontrib><creatorcontrib>Fujishima, Yuya</creatorcontrib><creatorcontrib>Kita, Shunbun</creatorcontrib><creatorcontrib>Minami, Satoshi</creatorcontrib><creatorcontrib>Sakaue, Taka-Aki</creatorcontrib><creatorcontrib>Nakamura, Yuto</creatorcontrib><creatorcontrib>Okita, Tomonori</creatorcontrib><creatorcontrib>Kawachi, Yusuke</creatorcontrib><creatorcontrib>Fukada, Shiro</creatorcontrib><creatorcontrib>Namba-Hamano, Tomoko</creatorcontrib><creatorcontrib>Takabatake, Yoshitsugu</creatorcontrib><creatorcontrib>Isaka, Yoshitaka</creatorcontrib><creatorcontrib>Nishizawa, Hitoshi</creatorcontrib><creatorcontrib>Ranscht, Barbara</creatorcontrib><creatorcontrib>Maeda, Norikazu</creatorcontrib><creatorcontrib>Shimomura, Iichiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; 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subjects Adipocytes
Adiponectin
Adiponectin - genetics
Animals
Cadherins
Cadherins - genetics
Capillaries
Capillary Permeability - genetics
Cells, Cultured
Damage
Glycosylphosphatidylinositol
Growth factors
Immunofluorescence
Injuries
Ischemia
Kidney diseases
Kidney Diseases - etiology
Kidney Diseases - genetics
Kidney Diseases - pathology
Kidney Tubules - pathology
Kidneys
Male
Mesenchyme
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscles
Pericytes
Permeability
Phenotypes
Platelet-derived growth factor
Progenitor cells
Proteins
Reperfusion
Reperfusion Injury - complications
Reperfusion Injury - genetics
Reperfusion Injury - pathology
Rodents
Severity of Illness Index
Stem cell transplantation
Stem cells
T-cadherin
title Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin
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