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Study: p21 facilitates chronic lung inflammation via epithelial and endothelial cells

p21 facilitates chronic lung inflammation via epithelial and endothelial cells
Accumulation of senescent cells is decreased in the lungs of p21-/- mice. WT and p21-/- mice were exposed to either PBS or aerosolized LPS (0.5 mg/ml), 3 times a week for 10 weeks. At 48 hours following the last LPS exposure, the lungs were harvested and frozen. Alternatively, lungs were harvested, fixed, and analyzed for markers of senescence. (A) Representative immunoblots for senescence-associated proteins p15, p16, p21 and p53 in the mice lungs. (B) mRNA expression levels of senescence markers p15, p16 and p21 in the mice lungs. (C, D) Immunohistochemistry (IHC) of lung sections for cleaved caspase 3, (C) and p21, (D). Scale bar represents 200μm. (E) SA-β-Gal staining of lung sections. Scale bar represents 200μm. (F) Quantification of the number of p21 positive cells per bronchial area, of the lung sections presented in (D). (G) Quantification of SA-β-gal (%) per bronchial area, of the lung sections presented in (E). Data information: Data were analyzed using one-way ANOVA, *P<0.05. **<0.005. ***P<0.0005 (B), and by Student’s t-test, *p<0.05, **p<0.01, and ***p<0.005 (F, G). Data represent mean ±SEM (A, n=3; B, n=3-10; CG, n=3-6 independent repeats). Credit: Aging (2023). DOI: 10.18632/aging.204622

A new research paper was published on the cover of Aging entitled, "p21 facilitates chronic lung inflammation via epithelial and endothelial cells."

Cellular senescence is a stable state of cell cycle arrest that regulates tissue integrity and protects the organism from tumorigenesis. However, the accumulation of senescent cells during aging contributes to age-related pathologies. One such pathology is chronic lung inflammation.

p21 (CDKN1A) regulates via inhibition of cyclin-dependent kinases (CDKs). However, its role in chronic lung inflammation and functional impact on , where senescent cells accumulate, is less understood.

In this new study, researchers Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, and Valery Krizhanovsky from the Weizmann Institute of Science aimed to elucidate the role of p21 in chronic lung inflammation.

"[...] we subjected p21 knockout (p21-/-) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to and accumulation of senescent cells," write the researchers.

The researchers utilized a lipopolysaccharide (LPS) inhalation-induced chronic bronchitis procedure to study the effects of repetitive LPS exposure on p21 knockout (p21-/-) mice. Furthermore, the team aimed to examine the specific contribution of the epithelial, endothelial and immune compartments to chronic bronchitis pathology.

They found that p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and , but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure.

The researchers conclude, "Therefore, we suggest that p21-dependent elimination of senescent cells may limit the damage induced by the pro-inflammatory presence of senescent cells, but also promote tissue regeneration. Therefore, inhibition of p21 represents a promising strategy for limiting age-related inflammatory disorders in general and obstructive lung diseases in particular."

More information: Naama Levi et al, p21 facilitates chronic lung inflammation via epithelial and endothelial cells, Aging (2023). DOI: 10.18632/aging.204622

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Citation: Study: p21 facilitates chronic lung inflammation via epithelial and endothelial cells (2023, April 17) retrieved 8 December 2023 from
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