The Journal of biological chemistryJul 28, 2026

Sugar-Modified CD147 Triggers Cell Cleanup to Reduce Fibroblast Activation and Transformation

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

CD147 expression is markedly downregulated in fibrotic lung tissues.

CD147, a glycosylated protein, may regulate pulmonary fibrosis through two distinct pathways.
Depletion of CD147 leads to enhanced activation, proliferation, and extracellular matrix production in fibroblasts.
CD147 is associated with promoting the formation of autophagosomes and the degradation of p62, which may aid in clearing pro-fibrotic factors.
The anti-fibrotic effects of CD147 depend on its glycosylation status; fully glycosylated CD147 can suppress the transformation of fibroblasts into myofibroblasts.
Non-glycosylated forms of CD147 do not exhibit regulatory capacity in fibrotic processes.

Simplified

Idiopathic pulmonary fibrosis (IPF) is a progressive and invariably fatal interstitial lung disease driven by persistent alveolar epithelial injury, which triggers aberrant fibroblast activation and pathological myofibroblast differentiation. In this study, we identify CD147-a heavily glycosylated transmembrane protein of the immunoglobulin superfamily-as a novel glycosylation-dependent regulator of pulmonary fibrosis operating through dual mechanistic pathways. CD147 expression was markedly downregulated in fibrotic lung tissues and predominantly localized to pulmonary fibroblasts. CD147 depletion significantly enhances fibroblast activation, proliferation, and extracellular matrix (ECM) production. Mechanistically, CD147 promotes autophagosome formation and facilitates p62 degradation, indicating its function in augmenting autophagic clearance of pro-fibrotic effectors. Notably, the anti-fibrotic activity of CD147 is strictly contingent upon its N-linked glycosylation status, the fully glycosylated CD147 robustly suppresses fibroblast-to-myofibroblast transformation and ECM deposition, while non-glycosylated isoforms are entirely devoid of this regulatory capacity. These findings provide compelling evidence that CD147 enhancing autophagic clearance of pro-fibrotic effectors and suppress the fibrotic progression through glycosylation-dependent mechanisms.

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Sugar-Modified CD147 Triggers Cell Cleanup to Reduce Fibroblast Activation and Transformation

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