Evidence map›Paper›PMID 34645789›Full record

ArticleCell death & disease2021

The interaction of S100A16 and GRP78 actives endoplasmic reticulum stress-mediated through the IRE1α/XBP1 pathway in renal tubulointerstitial fibrosis.

Runbing Jin, Anran Zhao, Shuying Han, Dan Zhang, Hui Sun, Min Li, Dongming Su, Xiubin Liang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
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  13. Poricoic acid A attenuates renal fibrosis by inhibiting endoplasmic reticulum stress-mediated apoptosis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024
    Article
  14. Article
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  16. Article
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  19. International journal of biological sciences · 2023
    Article
  20. Gut dysbacteriosis attenuates resistance toEmerging microbes & infections · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Runbing Jin *Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.
Anran Zhao *Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.
Shuying HanDepartment of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.
Dan ZhangDepartment of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.
Hui SunDepartment of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.
Min LiDepartment of Pathology, Nanjing Medical University, Nanjing, 211166, China.
Dongming SuDepartment of Pathology, Nanjing Medical University, Nanjing, 211166, China.
Xiubin LiangDepartment of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China. liangxiubin@njmu.edu.cn.ORCID 0000-0001-9169-0390
Nanjing Medical University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81570779National Natural Science Foundation of China (National Science Foundation of China) 81670619National Natural Science Foundation of China (National Science Foundation of China) 81870467
6 · The paper itself

Abstract

Recent studies have indicated that the development of acute and chronic kidney disease including renal fibrosis is associated with endoplasmic reticulum (ER) stress. S100 calcium-binding protein 16 (S100A16) as a novel member of the S100 family is involved in kidney disease; however, few studies have examined fibrotic kidneys for a relationship between S100A16 and ER stress. In our previous study, we identified GRP78 as a protein partner of S100A16 in HK-2 cells. Here, we confirmed a physical interaction between GRP78 and S100A16 in HK-2 cells and a markedly increased expression of GRP78 in the kidneys of unilateral ureteral occlusion mice. S100A16 overexpression in HK-2 cells by infection with Lenti-S100A16 also induced upregulation of ER stress markers, including GRP78, p-IRE1α, and XBP1s. Immunofluorescence staining demonstrated that the interaction between S100A16 and GRP78 predominantly occurred in the ER of control HK-2 cells. By contrast, HK-2 cells overexpressing S100A16 showed colocalization of S100A16 and GRP78 mainly in the cytoplasm. Pretreatment with BAPTA-AM, a calcium chelator, blunted the upregulation of renal fibrosis genes and ER stress markers induced by S100A16 overexpression in HK-2 cells and suppressed the cytoplasmic colocalization of GRP78 and S100A16. Co-immunoprecipitation studies suggested a competitive binding between S100A16 and IRE1α with GRP78 in HK-2 cells. Taken together, our findings demonstrate a significant increase in S100A16 expression in the cytoplasm following renal injury. GRP78 then moves into the cytoplasm and binds with S100A16 to promote the release of IRE1α. The subsequent phosphorylation of IRE1α then leads to XBP1 splicing that activates ER stress.

Indexed as

Endoplasmic Reticulum StressSignal TransductionAnimalsCalciumCell LineEndoplasmic Reticulum Chaperone BiPEndoribonucleasesFibrosisHumansKidneyMaleMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalProtein BindingCalciumEndoplasmic Reticulum Chaperone BiPEndoribonucleasesS100A16 protein, humanS100A16 protein, mouseS100 ProteinsTransforming Growth Factor beta1X-Box Binding Protein 1

Identifiers

PMID34645789
PMCPMC8514525
OpenAlexW3207689816

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.