Modulation of Gene Expression by Extracellular pH Variations in Human Fibroblasts: a Transcriptomic and Proteomic Study
Abstract
Homeostasis of the intracellular ionic concentration, in particular that of hydrogen ions, is pivotal to the maintenance of cell function and viability. Nonetheless, pH fluctuations in both the intracellular and the extracellular compartments can occurr during development, in physiological processes and in disease. The influence of pH variations on gene expression has been studied in different model systems, but only for a limited number of genes. We have performed a broad range analysis of the patterns of gene expression in normal human dermal fibroblasts at two different pH values (in the presence and in the absence of serum), with the aim of getting a deeper insight into the regulation of the transcriptional program as a response to a pH change. Using the Affymetrix gene chip system, we found that the expression of 2068 genes (out of 12 565) was modulated by more than two-fold at 24, 48 or 72 h after the shift of the culture medium pH to a more acidic value, stanniocalcin 1 being a remarkable example of a strongly up-regulated gene. Genes displaying a modulated pattern of expression included, among others, cell cycle regulators (consistent with the observation that acidic pH abolishes the growth of fibroblasts in culture) and relevant extracellular matrix (ECM) components. Extracellular matrix protein 2, a protein with a restricted pattern of expression in adult human tissues, was found to be remarkably overexpressed as a consequence of serum starvation. Since ECM componen…
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Reductions in medium pH (to pH 6.7) modulated the expression of 2,068 genes (out of 12,565) by more than two-fold after only 24 h of culture in human fibroblasts.
“A transcriptomic study, focusing on human fibroblasts, revealed that reductions in medium pH (to pH 6.7) modulated the expression of 2,068 genes (out of 12,565) by more than two-fold after only 24 h of culture (Bumke et al., 2003).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Bumke et al., 2003
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References 70 · Cited by 45
- Authors
- Bumke, M. A., Neri, D., & Elia, G.
- Affiliations
- ETH Zurich (CH)
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2003-05
- Volume
- 3
- Issue
- 5
- Pages
- 675-688
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- OpenAlex
- W2001799691
- Cited by
- 45
- References
- 70
- Citations by year
- 2026: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2012: 1
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PROTEOMICS (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- extracellular pH, low pH, human dermal fibroblasts, gene expression regulation, stanniocalcin-1, extracellular matrix proteins, serum deprivation, cell cycle regulators, secreted proteins, protein isoforms, agrin, tetranectin, vascular targeting, transcriptional response
- MeSH terms
- Cells, Cultured, Culture Media, Fibroblasts, Humans, Hydrogen-Ion Concentration, RNA, Messenger, Mass Spectrometry, Transcription, Genetic, Electrophoresis, Gel, Two-Dimensional, Gene Expression, Extracellular Matrix Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Proteomics, Extracellular Fluid
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