• Modeling Mechanism：

  Progesterone exacerbates pulmonary fibrosis through multiple mechanisms: ① It promotes myofibroblast activation (increased α-SMA expression) and increases collagen deposition; ② It upregulates the key fibrotic cytokine TGF-β, inhibits matrix metalloproteinase 9 (MMP9) activity, and disrupts the degradation balance of the extracellular matrix (ECM); ③ It inhibits systemic inflammation (reducing serum TNF-α) while increasing cortisol levels, promoting excessive tissue repair through the imbalance of "anti-inflammatory-fibrotic"; ④ It directly induces subpleural fibrosis in normal lung tissue and, under pathological conditions, synergistically exacerbates damage with bleomycin.

• Related Products：

  Progesterone (T0478)

• Modeling Method：

  Experimental Subject：

  Mice: BALB/c strain, female, 6–8 weeks old, approximate body weight 20 g

  Dosage and Administration Route：

  ① Fibrosis induction: Bleomycin (1.5 U/mL) at 0.075 U/g administered via subcutaneous injection in the back, once daily for 28 days;
  ② Progesterone intervention:
  - Synchronised intervention group (BLM+P28): 1 mg/animal (50 μg/g) progesterone, subcutaneous injection, initiated concurrently with bleomycin, for 28 days;
  - Delayed intervention group (BLM+P21): 1 mg/animal progesterone, subcutaneous injection, initiated one week after bleomycin injection, for 21 days;
  ③ Control Groups: Pure bleomycin group (BLM), pure progesterone group (P21/P28), PBS control group

  Dosing Frequency and Duration Model：

  Bleomycin administered once daily for 28 days
  Progesterone intervention once daily for 21 or 28 days

• Validation：

  Histological markers: Fibrosis degree: Masson trichrome staining showed significantly increased collagen deposition in the lung tissue of the BLM+P28 group (P<0.0001), while subpleural fibrosis was observed in the progesterone-only group (P28) (P<0.001); Molecular markers: Increased expression of α-SMA (P<0.01) and TGF-β (P<0.05) and decreased MMP9 activity (P<0.05) in the lung tissue of the BLM+P28 group, and downregulated expression of Col1a2, Ctgf, and Edn1 genes; Serum markers: Decreased TNF-α level (P<0.05) and increased cortisol level (P<0.05) in the BLM+P group; Specificity verification: Hydroxyproline detection showed increased hydroxyproline content in the lung tissue of the BLM+P28 group (P<0.05), consistent with the collagen deposition results, confirming the aggravation of fibrosis.

*Precautions： At the end of the study, the lung and injured skin were removed under deep anesthesia.

*References：Vafashoar F,et,al. Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis. Front Immunol. 2021 Nov 29;12:742227.