ArticleCellular and molecular life sciences : CMLS2026
Matrix stiffness induced CREB3L1 activation contributed to skin fibrosis through calcium influx triggered endoplasmic reticulum stress.
Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundSkin fibrosis substantially contributes to morbidity and mortality. Fibrotic remodeling, characterized by accumulated and stiffened extracellular matrix, persistently exerts mechanical cues and consistently activates fibroblasts, implying biomechanics as a major driver of fibrosis. However, our understanding towards mechanisms of biomechanics induced fibrosis remained limited.
methodsIntegrated single-cell sequencing analysis was performed to reveal the atlas of fibrotic skin. ChIP sequencing was performed to reveal the binding sites of CREB3L1. Nanoindenter was used to identify the mechanical properties. Gel contraction assay, wound healing assay, and live cell imaging were conducted to assess the behavior of fibroblasts cultured on hydrogels of different rigidities. Bleomycin induced and mechanical loading induced skin fibrosis models were established on CREB3L1 knockdown and control mice.
resultsWe identified a mechanosensitive fibroblast cluster that exerts contraction and ECM deposition functions in fibrotic skin, and its transcriptional identity was maintained by CREB3L1. Elevated expression of CREB3L1 was confirmed in human and mouse fibrotic skin. Further analysis showed that CREB3L1 was required for fibroblast activation, including contraction, migration, and ECM accumulation. More importantly, we revealed that matrix stiffness could alter calcium homeostasis, causing calcium influx and endoplasmic reticulum stress. The ER stress state in turn triggered the cleavage of CREB3L1, releasing its luminal domain that function as a profibrotic transcription factor. Inhibiting CREB3L1 could alleviate skin fibrosis both in vivo and in vitro.
conclusionsThis study elucidates the molecular mechanism of CREB3L1 mechanosensitive activation in matrix stiffness induced skin fibrosis, and presents a promising therapeutic target for clinical translation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.